115 results on '"Martin N. Sillence"'
Search Results
2. Carbohydrate pellets to assess insulin dysregulation in horses
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Melody A. deLaat, Tobias Warnken, Julien Delarocque, Dania B. Reiche, Anne J. Grob, Karsten Feige, Harry B. Carslake, Andy E. Durham, Martin N. Sillence, Kristen E. Thane, Nicholas Frank, Johan Brojer, Sanna Lindase, and Johanna Sonntag
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equine metabolic syndrome ,horse ,hyperinsulinemia ,laminitis ,oral glucose test ,palatability ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background A glycemic challenge test is used for the diagnosis of insulin dysregulation (ID) in horses and ponies. Different forms of the test exist where the administrative route and dose of glucose vary, which makes interpretation of results challenging. Hypothesis/Objectives To evaluate the palatability of, and blood glucose and insulin responses to, carbohydrate pellets fed as an oral glucose test (OGT), and to establish the diagnostic threshold for ID when using the pellets. Animals University and privately‐owned horses and ponies (n = 157) comprised of 31 breeds and both sexes. Methods Multicenter cohort study. A custom‐produced glycemic pellet was offered for free intake at 0.5 g/kg BW soluble carbohydrate and serum insulin and blood glucose concentrations measured before and after (60, 120, and 180 minutes) the pellets were offered. Pellet acceptance and intake time (those that finished within 10 minutes) were determined to assess palatability. Results The pellets were palatable to 132/157 animals, and ponies found the pellets more (P = .004) palatable than horses. The median intake time (4 [3‐6] minutes) was positively correlated with acceptance grade (r = .51; P
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- 2023
- Full Text
- View/download PDF
3. Metabolic profile distinguishes laminitis-susceptible and -resistant ponies before and after feeding a high sugar diet
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Julien Delarocque, Dania B. Reiche, Alexandra D. Meier, Tobias Warnken, Karsten Feige, and Martin N. Sillence
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Laminitis ,Equine metabolic syndrome ,Pituitary pars intermedia dysfunction ,Metabolome ,Biomarker ,Insulin dysregulation ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background Insulin dysregulation (ID) is a key risk factor for equine endocrinopathic laminitis, but in many cases ID can only be assessed accurately using dynamic tests. The identification of other biomarkers could provide an alternative or adjunct diagnostic method, to allow early intervention before laminitis develops. The present study characterised the metabolome of ponies with varying degrees of ID using basal and postprandial plasma samples obtained during a previous study, which examined the predictive power of blood insulin levels for the development of laminitis, in ponies fed a high-sugar diet. Samples from 10 pre-laminitic (PL – subsequently developed laminitis) and 10 non-laminitic (NL – did not develop laminitis) ponies were used in a targeted metabolomic assay. Differential concentration and pathway analysis were performed using linear models and global tests. Results Significant changes in the concentration of six glycerophospholipids (adj. P ≤ 0.024) and a global enrichment of the glucose-alanine cycle (adj. P = 0.048) were found to characterise the response of PL ponies to the high-sugar diet. In contrast, the metabolites showed no significant association with the presence or absence of pituitary pars intermedia dysfunction in all ponies. Conclusions The present results suggest that ID and laminitis risk are associated with alterations in the glycerophospholipid and glucose metabolism, which may help understand and explain some molecular processes causing or resulting from these conditions. The prognostic value of the identified biomarkers for laminitis remains to be investigated in further metabolomic trials in horses and ponies.
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- 2021
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4. The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies
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Danielle M. Fitzgerald, Christopher C. Pollitt, Donald M. Walsh, Martin N. Sillence, and Melody A. de Laat
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Equine metabolic syndrome ,Fertiliser ,Horse ,Hyperinsulinaemia ,Insulin dysregulation ,Laminitis ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background The oral glucose test (OGT) is a useful tool for diagnosing insulin dysregulation (ID) and is somewhat repeatable in ponies under consistent management. This study aimed to determine whether the insulin and incretin responses to an OGT in ponies differed after short-term access to fertilised pasture, compared to unfertilised pasture, by using a randomised, repeated measures study design. Sixteen mixed-breed ponies were classified as severely insulin-dysregulated (SD; post-prandial insulin ≥80 μIU/mL) or not severely insulin-dysregulated (NSD; post-prandial insulin
- Published
- 2019
- Full Text
- View/download PDF
5. Incidence and risk factors for recurrence of endocrinopathic laminitis in horses
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Melody A. deLaat, Dania B. Reiche, Martin N. Sillence, and James M. McGree
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ACTH ,equine metabolic syndrome ,horse ,hyperinsulinemia ,insulin dysregulation ,pituitary pars intermedia dysfunction ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background Endocrinopathic laminitis is common in horses and ponies, but the recurrence rate of the disease is poorly defined. Objectives To determine the incidence of, and risk factors for, the recurrence of endocrinopathic laminitis. Animals Privately owned horses and ponies with acute laminitis (n = 317, of which 276 cases with endocrinopathic laminitis were followed up to study completion). Methods This prospective cohort study collected data on veterinary‐diagnosed cases of acute laminitis for 2 years. Each case was classified on acceptance to the study as endocrinopathic or non‐endocrinopathic using data collected in a questionnaire completed by the animal's veterinarian. Follow‐up data were collected at regular intervals to determine whether the laminitis recurred in the 2‐year period after diagnosis. Results The recurrence rate for endocrinopathic laminitis was 34.1%. The risk of recurrence during the 2‐year study period increased with basal, fasted serum insulin concentration (P ≤ .05), with the probability of recurrence increasing markedly as the insulin concentration increased beyond the normal range (0‐20 μIU/mL) to over the threshold for normal (up to approximately 45 μIU/mL). Being previously diagnosed with laminitis (before the study; P = .05) was also a risk factor for recurrent laminitis. Cases with a higher Obel grade of laminitis were likely (P = .05) to recur sooner. Conclusions and clinical importance Knowing that hyperinsulinemia and being previously diagnosed with laminitis are significant risk factors for recurrence will enable clinicians to proactively address these factors, thereby potentially reducing the risk of recurrence of laminitis.
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- 2019
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6. Phenotypic, hormonal, and clinical characteristics of equine endocrinopathic laminitis
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Melody A. deLaat, Martin N. Sillence, and Dania B. Reiche
- Subjects
ACTH ,equine metabolic syndrome ,horse ,hyperinsulinemia ,pituitary pars intermedia dysfunction ,Veterinary medicine ,SF600-1100 - Abstract
Background Equine endocrinopathic laminitis is common and can be associated with an underlying endocrinopathy, such as equine metabolic syndrome (EMS), pituitary pars intermedia dysfunction (PPID), pasture consumption, or any combination of these factors. Objectives The aim of the study was to improve the risk assessment capabilities of clinicians, and to inform management strategies, for acute endocrinopathic laminitis by prospectively examining the phenotypic, hormonal, and clinical characteristics of the disease in a large cohort. Animals Privately owned horses and ponies (n = 301) of any age, sex, or breed diagnosed with laminitis by a veterinarian. A history of laminitis was acceptable. Methods This was a prospective cohort study. Veterinarians provided information on each case via an online questionnaire after informed consent from the animal's owner, and all data were de‐identified before analysis. Serum insulin and plasma adrenocorticotrophic hormone concentrations were measured in each case. Results Most cases were recruited in spring (109/301; 36.2%). Concurrent EMS and PPID resulted in higher basal insulin concentrations (49 [21.5‐141]; P
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- 2019
- Full Text
- View/download PDF
7. Insulin and incretin responses to grazing in insulin‐dysregulated and healthy ponies
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Danielle M. Fitzgerald, Donald M. Walsh, Martin N. Sillence, Christopher C. Pollitt, and Melody A. deLaat
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equine metabolic syndrome ,glucagon‐like peptide‐1 ,glucose‐dependent insulinotropic polypeptide ,hyperinsulinemia ,laminitis ,pasture ,Veterinary medicine ,SF600-1100 - Abstract
Background Supraphysiological insulin and incretin responses to a cereal‐based diet have been described in horses and ponies with insulin dysregulation (ID). However, the hormonal responses to grazing have not yet been described. Objectives To determine if there is a difference in the insulin and incretin responses to grazing pasture between insulin‐dysregulated and healthy ponies. Animals A cohort of 16 ponies comprising 5 with normal insulin regulation (NIR), 6 with moderate ID (MID), and 5 with severe ID (SID). Methods In this case‐control study, an oral glucose test (OGT) was used to determine the insulin responsiveness of each pony to PO carbohydrate before grazing pasture (4 hours) for 3 consecutive days. Serial blood samples collected during grazing were analyzed for glucose, insulin, glucose‐dependent insulinotropic peptide (GIP) and active glucagon‐like peptide‐1 (aGLP‐1), and compared among pony groups and day of pasture access. Results The area under the insulin curve when grazing increased with ID severity (P
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- 2019
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8. Effects of an anti-IGF-1 receptor monoclonal antibody on laminitis induced by prolonged hyperinsulinaemia in Standardbred horses
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Samira Rahnama, Niveditha Vathsangam, Robert Spence, Carlos E. Medina-Torres, Christopher C. Pollitt, Melody A. de Laat, Simon R. Bailey, Martin N. Sillence, and Lisa M. Katz
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Medicine ,Science - Abstract
Currently, there are no registered veterinary drugs for the treatment of endocrinopathic equine laminitis, and although this form of the disease is known to be caused by prolonged hyperinsulinaemia, the mechanism of insulin toxicity is unclear. One possibility is that high concentrations of insulin activate IGF-1 receptors (IGF-1R) in lamellar tissue, leading to uncontrolled cell proliferation and epidermal lamellar dysregulation. An equinized version of a human anti-IGF-1R therapeutic monoclonal antibody (mAb11) was generated to test this theory, using a modification of the prolonged euglycaemic-hyperinsulinaemic clamp technique. Healthy Standardbred horses were infused for 48 h with 0.9% saline (negative-control, n = 6), a combination of insulin (4.5 mIU/kgBW/min) and a variable infusion of 50% glucose to maintain euglycaemia (positive-control, n = 6), or insulin and glucose, preceded by a low dose of mAb11 (20 mg), designed to treat one foot only and delivered by retrograde infusion into one forelimb (mAb-treated, n = 7). Maximum insulin concentrations were 502 ± 54.4 and 435 ± 30.4 μIU/mL in the positive-control and mAb11-treated groups, respectively (P = 0.33). While the control group remained healthy, all the insulin-treated horses developed laminitis within 30 h, as judged by clinical examination, foot radiographs and histological analysis. Some effects of insulin were not attenuated by the antibody, however, relative to the positive-control group, horses treated with mAb11 showed less sinking of the distal phalanx (P < 0.05) and milder histological changes, with markedly less elongation at the tips of the secondary epidermal lamellae (P < 0.05). These differences were apparent in both front feet and were statistically significant when the values for both feet were combined. The results confirm that IGF-1R may have a role in insulin-induced laminitis and suggest that mAb11 warrants further research as a potential agent to prevent or treat the disease.
- Published
- 2020
9. A 'modified Obel' method for the severity scoring of (endocrinopathic) equine laminitis
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Alexandra Meier, Melody de Laat, Christopher Pollitt, Donald Walsh, James McGree, Dania B. Reiche, Marcella von Salis-Soglio, Luke Wells-Smith, Ulrich Mengeler, Daniel Mesa Salas, Susanne Droegemueller, and Martin N. Sillence
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Laminitis ,Lameness ,Diagnostics ,Horses ,Equine metabolic syndrome ,Insulin ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background Laminitis is a common equine disease characterized by foot pain, and is commonly diagnosed using a five-grade Obel system developed in 1948 using sepsis-related cases. However, endocrinopathic laminitis is now the most common form of the disease and clinical signs may be mild, or spread across two Obel grades. This paper describes a modified method which assigns scores to discreet clinical signs, providing a wider scale suitable for use in a research setting. Methods The “modified Obel” method was developed using an iterative process. First, a prototype method was developed during the detailed observation of 37 ponies undergoing a laminitis induction experiment. The final method was refined and validated using video footage taken during the induction study and from a clinical trial of naturally occurring endocrinopathic laminitis cases. The Obel method was deconstructed and key laminitis signs were evaluated to develop a three-stage, five criteria method that employs a severity scale of 0–12. Veterinarians (n = 28) were recruited to watch and assess 15 video recordings of cases of varying severity, using the Obel and “modified Obel” methods. The inter-observer agreement (reproducibility) was determined using Kendall’s coefficient of concordance (Kendall W) and Krippendorf’s alpha reliability coefficient. A total of 14 veterinarians repeated the exercise 2–4 weeks after their original assessment, to determine intra-observer agreement (repeatability), assessed using a weighted kappa statistic (kw). Agreement between methods was calculated by converting all “modified Obel” scores to Obel grades and calculating the mean and distribution of the differences. Results The “modified Obel” and Obel methods showed excellent and similar inter-observer agreement based on the Kendall W value (0.87, P < 0.001 vs. 0.85, P < 0.001) and Krippendorf’s alpha (95% CI) value (0.83 [0.53–0.90] vs. 0.77 [0.55–0.85]). Based on the kw value, the “modified Obel” method also had substantial repeatability, although slightly less than the Obel method, (0.80 vs. 0.91). Excellent agreement between the methods was found, with the mean difference (95% CI), comparing the Obel grade, with the “modified Obel” score converted to an Obel grade, being −0.12 (−0.19 to −0.06) grades. The Obel and converted “modified Obel” grades were identical 62% of the time (259/420) and a difference of one grade (higher or lower) occurred in 35% of cases (148/420). Conclusion Both methods show excellent agreement, reproducibility and repeatability when used to diagnose endocrinopathic laminitis. The “modified Obel” method is a three-step examination process for severity-scoring of endocrinopathic laminitis, initially proposed for use within a research setting. When using the modified method a diagnosis of laminitis also requires clinical acumen. The allocation of scores for specific clinical signs should be particularly useful in research trials monitoring laminitis recovery.
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- 2019
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10. Equine glucagon-like peptide-1 receptor physiology
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Murad H. Kheder, Simon R. Bailey, Kevin J. Dudley, Martin N. Sillence, and Melody A. de Laat
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Equine metabolic syndrome ,GLP-1 receptor ,Horse ,Insulin ,Incretin ,Laminitis ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background Equine metabolic syndrome (EMS) is associated with insulin dysregulation, which often manifests as post-prandial hyperinsulinemia. Circulating concentrations of the incretin hormone, glucagon-like peptide-1 (GLP-1) correlate with an increased insulin response to carbohydrate intake in animals with EMS. However, little is known about the equine GLP-1 receptor (eGLP-1R), or whether GLP-1 concentrations can be manipulated. The objectives were to determine (1) the tissue localisation of the eGLP-1R, (2) the GLP-1 secretory capacity of equine intestine in response to glucose and (3) whether GLP-1 stimulated insulin secretion from isolated pancreatic islets can be attenuated. Methods Archived and abattoir-sourced tissues from healthy horses were used. Reverse transcriptase PCR was used to determine the tissue distribution of the eGLP-1R gene, with immunohistochemical confirmation of its pancreatic location. The GLP-1 secretion from intestinal explants in response to 4 and 12 mM glucose was quantified in vitro. Pancreatic islets were freshly isolated to assess the insulin secretory response to GLP-1 agonism and antagonism in vitro, using concentration-response experiments. Results The eGLP-1R gene is widely distributed in horses (pancreas, heart, liver, kidney, duodenum, digital lamellae, tongue and gluteal skeletal muscle). Within the pancreas the eGLP-1R was immunolocalised to the pancreatic islets. Insulin secretion from pancreatic islets was concentration-dependent with human GLP-1, but not the synthetic analogue exendin-4. The GLP-1R antagonist exendin 9-39 (1 nM) reduced (P = 0.08) insulin secretion by 27%. Discussion The distribution of the eGLP-1R across a range of tissues indicates that it may have functions beyond insulin release. The ability to reduce insulin secretion, and therefore hyperinsulinemia, through eGLP-1R antagonism is a promising and novel approach to managing equine insulin dysregulation.
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- 2018
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11. Carbohydrate pellets to assess insulin dysregulation in horses
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Melody A. de Laat, Tobias Warnken, Julien Delarocque, Dania B. Reiche, Anne J. Grob, Karsten Feige, Harry B. Carslake, Andy E. Durham, Martin N. Sillence, Kristen E. Thane, Nicholas Frank, Johan Brojer, Sanna Lindase, and Johanna Sonntag
- Subjects
General Veterinary - Abstract
A glycemic challenge test is used for the diagnosis of insulin dysregulation (ID) in horses and ponies. Different forms of the test exist where the administrative route and dose of glucose vary, which makes interpretation of results challenging.To evaluate the palatability of, and blood glucose and insulin responses to, carbohydrate pellets fed as an oral glucose test (OGT), and to establish the diagnostic threshold for ID when using the pellets.University and privately-owned horses and ponies (n = 157) comprised of 31 breeds and both sexes.Multicenter cohort study. A custom-produced glycemic pellet was offered for free intake at 0.5 g/kg BW soluble carbohydrate and serum insulin and blood glucose concentrations measured before and after (60, 120, and 180 minutes) the pellets were offered. Pellet acceptance and intake time (those that finished within 10 minutes) were determined to assess palatability.The pellets were palatable to 132/157 animals, and ponies found the pellets more (P = .004) palatable than horses. The median intake time (4 [3-6] minutes) was positively correlated with acceptance grade (r = .51; P .0001). Consumption of the pellets elicited peak blood glucose (6.6 [5.8-7.8] mmol/L) and serum insulin (40.5 [19-99.8] μIU/mL) responses at 120 minutes. At 120 minutes the optimal cut-off was 83 μIU/mL (95% CI: 70-99 μIU/mL) for the IMMULITE 2000XPi assay.The pellets were palatable and a suitable, novel carbohydrate source for the OGT.
- Published
- 2022
12. A starch-rich treat affects enteroinsular responses in ponies
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Poppy E. M. Sibthorpe, Danielle M. Fitzgerald, Lan Chen, Martin N. Sillence, and Melody A. de Laat
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Blood Glucose ,Xylose ,General Veterinary ,Animals ,Insulin ,Starch ,Horses ,Diet - Abstract
OBJECTIVE To determine the effect of a starch-rich treat, added to the daily diet of ponies for 10 days, on enteroinsular responses to meal consumption. ANIMALS 10 mixed-breed adult ponies owned by Queensland University of Technology were used in the study. Six ponies were metabolically healthy, and 4 were insulin dysregulated at the start of the study, according to the results of an in-feed oral glucose test. PROCEDURES A bread-based treat was offered twice daily for 10 days, adding 0.36 ± 0.04 g/kg body weight (BW) carbohydrates to the daily diet. Before and after treatment, the intestinal capacity for simple carbohydrate absorption was approximated with a modified D-xylose absorption test. Plasma glucagon-like peptide-2 (GLP-2), blood glucose, and serum insulin responses to eating were also measured before and after treatment. RESULTS The absorption of D-xylose (area under the curve [AUC]) increased 1.6-fold (P < .001) after 10 days of eating the treat. In addition, while basal (fasted) GLP-2 concentrations were not affected, GLP-2 AUC increased 1.4-fold in response to eating (P = .005). The treat did not change blood glucose or serum insulin concentrations, before, during, or after eating. CLINICAL RELEVANCE A small amount of additional carbohydrate each day in the form of a treat can cause a measurable change in the enteroinsular responses to eating.
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- 2022
13. Association between insulin dysregulation and adrenocorticotropic hormone in aged horses and ponies with no clinical signs of pituitary pars intermedia dysfunction
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Fang I. Li, Robert J. Spence, Melody A. de Laat, Patricia A. Harris, Johanna Sonntag, Nicola J. Menzies‐Gow, Andy E. Durham, Simon R. Bailey, and Martin N. Sillence
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General Medicine - Published
- 2023
14. Author response for 'Association between insulin dysregulation and <scp>ACTH</scp> in aged horses and ponies with no clinical signs of <scp>PPID</scp>'
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null Fang I. Li, null Robert J. Spence, null Melody A. de Laat, null Patricia A. Harris, null Johanna Sonntag, null Nicola J. Menzies‐Gow, null Andy E. Durham, null Simon R. Bailey, and null Martin N. Sillence
- Published
- 2022
15. The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies
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Dania Birte Reiche, Martin N. Sillence, Alexandra Meier, M.A. de Laat, and Danielle M. Fitzgerald
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medicine.medical_specialty ,Laminitis ,040301 veterinary sciences ,medicine.medical_treatment ,Cmax ,Placebo ,0403 veterinary science ,Random Allocation ,03 medical and health sciences ,Hyperinsulinism ,Internal medicine ,Equine metabolic syndrome ,Nitriles ,Hyperinsulinemia ,medicine ,Animals ,Hypoglycemic Agents ,Insulin ,Horses ,Sodium-glucose linked transport inhibitor ,030304 developmental biology ,0303 health sciences ,Meal ,lcsh:Veterinary medicine ,General Veterinary ,business.industry ,04 agricultural and veterinary sciences ,General Medicine ,medicine.disease ,Transport inhibitor ,Treatment Outcome ,Endocrinology ,lcsh:SF600-1100 ,Horse Diseases ,business ,Research Article - Abstract
Background A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 μIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo (n = 10–12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal. Results Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 μIU/mL in wk. 0, to 119 ± 19 μIU/mL (P = 0.015) and 117 ± 15 μIU/ml (P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin Cmax in this group was not significantly lower than in controls at wk-8 (P = 0.061), it was lower at wk-16 (P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin Cmax returned to 199 ± 36 μIU/mL in the treated group, with no rebound effect. Conclusions Velagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them. Electronic supplementary material The online version of this article (10.1186/s12917-019-1811-2) contains supplementary material, which is available to authorized users.
- Published
- 2019
16. Phenotypic, hormonal, and clinical characteristics of equine endocrinopathic laminitis
- Author
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Martin N. Sillence, Dania Birte Reiche, and Melody A. de Laat
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Male ,medicine.medical_specialty ,Hoof and Claw ,040301 veterinary sciences ,medicine.medical_treatment ,Standard Article ,030204 cardiovascular system & hematology ,Endocrine System Diseases ,0403 veterinary science ,Cohort Studies ,Foot Diseases ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Adrenocorticotropic Hormone ,Metabolic Diseases ,Internal medicine ,Pituitary pars intermedia dysfunction ,medicine ,Hyperinsulinemia ,Animals ,Body Size ,Insulin ,Horses ,Prospective Studies ,Prospective cohort study ,lcsh:Veterinary medicine ,General Veterinary ,business.industry ,Horse ,04 agricultural and veterinary sciences ,Laminitis ,medicine.disease ,equine metabolic syndrome ,Standard Articles ,ACTH ,horse ,Diet ,Equine metabolic syndrome ,pituitary pars intermedia dysfunction ,Lameness ,hyperinsulinemia ,lcsh:SF600-1100 ,Female ,Horse Diseases ,EQUID ,business - Abstract
BACKGROUND: Equine endocrinopathic laminitis is common and can be associated with an underlying endocrinopathy, such as equine metabolic syndrome (EMS), pituitary pars intermedia dysfunction (PPID), pasture consumption, or any combination of these factors. OBJECTIVES: The aim of the study was to improve the risk assessment capabilities of clinicians, and to inform management strategies, for acute endocrinopathic laminitis by prospectively examining the phenotypic, hormonal, and clinical characteristics of the disease in a large cohort. ANIMALS: Privately owned horses and ponies (n = 301) of any age, sex, or breed diagnosed with laminitis by a veterinarian. A history of laminitis was acceptable. METHODS: This was a prospective cohort study. Veterinarians provided information on each case via an online questionnaire after informed consent from the animal's owner, and all data were de‐identified before analysis. Serum insulin and plasma adrenocorticotrophic hormone concentrations were measured in each case. RESULTS: Most cases were recruited in spring (109/301; 36.2%). Concurrent EMS and PPID resulted in higher basal insulin concentrations (49 [21.5‐141]; P
- Published
- 2019
17. The application of a new laminitis scoring method to model the rate and pattern of improvement from equine endocrinopathic laminitis in a clinical setting
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R. Klee, James McGree, J. Preuß, Martin N. Sillence, Dania Birte Reiche, Alexandra Meier, and M.A. de Laat
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Male ,Hoof and Claw ,medicine.medical_specialty ,Laminitis ,040301 veterinary sciences ,Lameness, Animal ,Physical examination ,Disease ,Severity of Illness Index ,Foot Diseases ,0403 veterinary science ,03 medical and health sciences ,Obel ,Germany ,Hyperinsulinism ,Equine metabolic syndrome ,Internal medicine ,Diagnosis ,Animals ,Insulin ,Medicine ,Horses ,030304 developmental biology ,0303 health sciences ,lcsh:Veterinary medicine ,General Veterinary ,medicine.diagnostic_test ,business.industry ,Scoring methods ,04 agricultural and veterinary sciences ,General Medicine ,Gait ,Natural history ,Disease Progression ,lcsh:SF600-1100 ,Female ,Horse Diseases ,business ,Foot (unit) ,Research Article - Abstract
Background Endocrinopathic, or hyperinsulinaemia-associated laminitis (HAL) is a common and debilitating equine foot disease, and although no pharmacological treatments are registered, several are under development. To evaluate the effect of such treatments, an accurate and consistent method is needed to track the clinical signs of laminitis over time, and the natural history of the disease, in terms of a ‘normal’ pattern of improvement, needs to be understood. This study examined the improvement pattern in clinical cases of naturally-occurring HAL subjected to a range of best-practice interventions, using two different scoring methods. Eighty horses and ponies with suspected HAL were enrolled in a study conducted at 16 veterinary practices across Germany. The severity of laminitis was assessed by independent veterinarians using both the traditional Obel method and a modified Obel method developed by Meier and colleagues. Assessments were made on the day of diagnosis (d 0), then on days 4, 9, 14, 25 and 42 during the intervention period. Pain medications were withheld for 24 h prior to clinical examination in all cases. Results Time to marked improvement from laminitis varied between individuals, but was difficult to monitor accurately using the Obel method, with the median grade being 2/4 on days 0 and 4, then 0/4 from d 9 onwards. More subtle changes could be identified using the Meier method, however, and the median scores were seen to follow the form of an exponential decay model in most horses, improving from 8/12 on d 0, to 0/12 on d 25. Within this composite scoring method, considerable variation was observed in the rate of improvement of individual clinical signs, with the average time taken for each sign to reach a median score of 0 ranging from 4 days (foot lift and weight shifting) to 25 days (gait when turned in a circle) across all 80 horses. Conclusions The Meier method provides a reliable and consistent method for monitoring the clinical status of horses with HAL, and despite the variability, the pattern of improvement described here should provide a useful benchmark against which individual cases and new treatments can be assessed.
- Published
- 2021
18. Active learning in the time of the pandemic: Report from the eye of the storm
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Christine Devine, Oliver Gaede, Martin N. Sillence, Andrew Fielding, Christoph Schrank, and Iwona Czaplinski
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Medical education ,Coronavirus disease 2019 (COVID-19) ,Salient ,Perception ,media_common.quotation_subject ,Active learning ,Pandemic ,Exceptional circumstances ,Psychology ,Effective teaching ,Learning design ,media_common - Abstract
This study investigated second- and third-year science students’ perceptions of the effectiveness of their learning practices during the COVID-19 pandemic. The study focused on the concept of active learning, with special attention paid to self-regulation and self-direction. The data collected through mixed research methods provided evidence of students’ flexible adjustment to the exceptional circumstances. However, the data also revealed a relatively limited range of learning strategies reported by respondents. Thus, this paper identifies an important need for further investigation of students’ practices to enhance their awareness of learning strategies, as a way of becoming active learners. Finally, the study also made salient the need for teacher training in effective teaching strategies, as a complementary strategy to promote students’ active learning. The conclusions from the study reach beyond the current circumstances, as they suggest implications for learning design in terms of educators’ training and designing for active learning.
- Published
- 2020
19. Metabolic profile distinguishes laminitis-susceptible and -resistant ponies before and after feeding a high sugar diet
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Julien, Delarocque, Dania B, Reiche, Alexandra D, Meier, Tobias, Warnken, Karsten, Feige, and Martin N, Sillence
- Subjects
Blood Glucose ,Male ,Hoof and Claw ,Laminitis ,Glycerophospholipids ,Biomarker ,Insulin dysregulation ,Diet ,Foot Diseases ,Risk Factors ,Equine metabolic syndrome ,Dietary Carbohydrates ,Metabolome ,Animals ,Insulin ,Female ,Horse Diseases ,Disease Susceptibility ,Horses ,Pituitary pars intermedia dysfunction ,Disease Resistance ,Research Article - Abstract
Background Insulin dysregulation (ID) is a key risk factor for equine endocrinopathic laminitis, but in many cases ID can only be assessed accurately using dynamic tests. The identification of other biomarkers could provide an alternative or adjunct diagnostic method, to allow early intervention before laminitis develops. The present study characterised the metabolome of ponies with varying degrees of ID using basal and postprandial plasma samples obtained during a previous study, which examined the predictive power of blood insulin levels for the development of laminitis, in ponies fed a high-sugar diet. Samples from 10 pre-laminitic (PL – subsequently developed laminitis) and 10 non-laminitic (NL – did not develop laminitis) ponies were used in a targeted metabolomic assay. Differential concentration and pathway analysis were performed using linear models and global tests. Results Significant changes in the concentration of six glycerophospholipids (adj. P ≤ 0.024) and a global enrichment of the glucose-alanine cycle (adj. P = 0.048) were found to characterise the response of PL ponies to the high-sugar diet. In contrast, the metabolites showed no significant association with the presence or absence of pituitary pars intermedia dysfunction in all ponies. Conclusions The present results suggest that ID and laminitis risk are associated with alterations in the glycerophospholipid and glucose metabolism, which may help understand and explain some molecular processes causing or resulting from these conditions. The prognostic value of the identified biomarkers for laminitis remains to be investigated in further metabolomic trials in horses and ponies. Supplementary Information The online version contains supplementary material available at 10.1186/s12917-021-02763-7.
- Published
- 2020
20. Effects of an anti-IGF-1 receptor monoclonal antibody on laminitis induced by prolonged hyperinsulinaemia in Standardbred horses
- Author
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Simon R. Bailey, Carlos E. Medina-Torres, Melody A. de Laat, Niveditha Vathsangam, Robert J. Spence, Christopher C. Pollitt, Martin N. Sillence, and Samira Rahnama
- Subjects
Physiology ,medicine.medical_treatment ,Cancer Treatment ,Biochemistry ,Receptor, IGF Type 1 ,Geographical Locations ,0403 veterinary science ,Endocrinology ,Immune Physiology ,Medicine and Health Sciences ,Insulin ,Receptor ,Saline ,Mammals ,Immune System Proteins ,Multidisciplinary ,Organic Compounds ,Monosaccharides ,Antibodies, Monoclonal ,Eukaryota ,04 agricultural and veterinary sciences ,Laminitis ,Antibodies, Anti-Idiotypic ,3. Good health ,Chemistry ,Oncology ,Vertebrates ,Physical Sciences ,Monoclonal ,Toxicity ,Medicine ,Anatomy ,Research Article ,medicine.medical_specialty ,Histology ,040301 veterinary sciences ,Science ,Equines ,Immunology ,Oceania ,Carbohydrates ,Pain ,Antibodies ,Signs and Symptoms ,Antibody Therapy ,Hyperinsulinism ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Horses ,Cell Proliferation ,Diabetic Endocrinology ,business.industry ,Organic Chemistry ,Organisms ,Chemical Compounds ,Australia ,0402 animal and dairy science ,Biology and Life Sciences ,Proteins ,medicine.disease ,040201 dairy & animal science ,Hormones ,Monoclonal Antibodies ,Glucose ,Amniotes ,People and Places ,Horse Diseases ,Clinical Immunology ,Epidermis ,Clinical Medicine ,business ,Zoology - Abstract
Currently, there are no registered veterinary drugs for the treatment of endocrinopathic equine laminitis, and although this form of the disease is known to be caused by prolonged hyperinsulinaemia, the mechanism of insulin toxicity is unclear. One possibility is that high concentrations of insulin activate IGF-1 receptors (IGF-1R) in lamellar tissue, leading to uncontrolled cell proliferation and epidermal lamellar dysregulation. An equinized version of a human anti-IGF-1R therapeutic monoclonal antibody (mAb11) was generated to test this theory, using a modification of the prolonged euglycaemic-hyperinsulinaemic clamp technique. Healthy Standardbred horses were infused for 48 h with 0.9% saline (negative-control, n = 6), a combination of insulin (4.5 mIU/kgBW/min) and a variable infusion of 50% glucose to maintain euglycaemia (positive-control, n = 6), or insulin and glucose, preceded by a low dose of mAb11 (20 mg), designed to treat one foot only and delivered by retrograde infusion into one forelimb (mAb-treated, n = 7). Maximum insulin concentrations were 502 ± 54.4 and 435 ± 30.4 μIU/mL in the positive-control and mAb11-treated groups, respectively (P = 0.33). While the control group remained healthy, all the insulin-treated horses developed laminitis within 30 h, as judged by clinical examination, foot radiographs and histological analysis. Some effects of insulin were not attenuated by the antibody, however, relative to the positive-control group, horses treated with mAb11 showed less sinking of the distal phalanx (P < 0.05) and milder histological changes, with markedly less elongation at the tips of the secondary epidermal lamellae (P < 0.05). These differences were apparent in both front feet and were statistically significant when the values for both feet were combined. The results confirm that IGF-1R may have a role in insulin-induced laminitis and suggest that mAb11 warrants further research as a potential agent to prevent or treat the disease.
- Published
- 2020
21. The effect of diet change and insulin dysregulation on the fecal microbiome of ponies
- Author
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Peter J. Prentis, Robert J. Spence, Danielle M. Fitzgerald, Melody A. de Laat, Martin N. Sillence, and Zachary K. Stewart
- Subjects
0301 basic medicine ,040301 veterinary sciences ,Physiology ,Firmicutes ,Aquatic Science ,0403 veterinary science ,Feces ,03 medical and health sciences ,Animal science ,RNA, Ribosomal, 16S ,biology.animal ,Grazing ,Animals ,Insulin ,Horses ,Microbiome ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,biology ,Pony ,Microbiota ,Bacteroidetes ,04 agricultural and veterinary sciences ,biology.organism_classification ,Diet ,030104 developmental biology ,Equine metabolic syndrome ,Insect Science ,Hay ,Animal Science and Zoology - Abstract
The equine microbiome can change in response to dietary alteration and might play a role in insulin dysregulation. The aim of this study was to determine the effect of adding pasture to a hay diet on the fecal bacterial microbiome of both healthy and insulin-dysregulated ponies. Fecal samples were collected from sixteen ponies before and after dietary change to enable bacterial 16S rRNA sequencing of the V3-V4 region. The dominant phyla in all samples were the Firmicutes and Bacteroidetes. The evenness of the bacterial populations decreased after grazing pasture, and when a pony was moderately insulin-dysregulated (P=0.001). Evenness scores negatively correlated with post-prandial glucagon-like peptide-1 concentrations after a hay-only diet (r2;=-0.7, P=0.001). A change in diet explained 3% of fecal microbiome variability. We conclude that metabolically healthy ponies have greater microbial stability when challenged with a subtle dietary change, compared to moderately insulin-dysregulated ponies.
- Published
- 2020
22. Effects of insulin on IGF-1 receptors in equine lamellar tissue in vitro
- Author
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M.A. de Laat, Samira Rahnama, Simon R. Bailey, Stephen T. Anderson, Robert J. Spence, C.L. Baskerville, Christopher C. Pollitt, N. Vathsangam, and Martin N. Sillence
- Subjects
medicine.medical_specialty ,Hoof and Claw ,medicine.medical_treatment ,Blotting, Western ,Receptor, IGF Type 1 ,Dephosphorylation ,Tissue Culture Techniques ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Food Animals ,Internal medicine ,medicine ,Animals ,Insulin ,Horses ,Receptor ,Cell Proliferation ,030219 obstetrics & reproductive medicine ,biology ,Cell growth ,Chemistry ,0402 animal and dairy science ,Antibodies, Monoclonal ,04 agricultural and veterinary sciences ,Laminitis ,040201 dairy & animal science ,In vitro ,Insulin receptor ,Gene Expression Regulation ,biology.protein ,Phosphorylation ,Animal Science and Zoology - Abstract
Although it is understood that equine endocrinopathic laminitis can be triggered by high concentrations of insulin, it is unclear whether this represents a direct action on lamellar tissue via insulin receptors (InsR), an interaction with IGF-1 receptors (IGF-1R), or some other, indirect action. This uncertainty is because of the reported scarcity of InsR in lamellar tissue and the low affinity of insulin for equine IGF-1R. In the present study, the effects of insulin and IGF-1 (as a positive control) were examined using lamellar explants isolated from the hooves of healthy horses and incubated in cell culture medium for between 2 min and 48 h. In this system, a low physiological concentration of IGF-1 (10 nM; 1.31 ng/mL) caused a marked increase in the appearance of phosphorylated IGF-1R after 5 min (P < 0.05), and this effect was blocked by a human anti-IGF-1R monoclonal antibody (mAb). However, a high concentration of insulin (10 nM; 1,430 μIU/mL) appeared to cause dephosphorylation of the IGF-1R after 5 min (P < 0.01), 15 min, and 30 min (P < 0.001). Using 3H-thymidine as a marker, it was also demonstrated that insulin and IGF-1-stimulated cell proliferation in lamellar explants over the same concentration range as each other (1-100 nM), implying that each peptide acts via its own receptor (P < 0.001). Conversely, the effect of both peptides could be blocked using a selective anti-IGF-1R mAb (P < 0.001), implying that insulin acts via IGF1-R (either directly or indirectly). Notwithstanding this conundrum, the results demonstrate that insulin acts directly on lamellar tissue and suggest that a therapeutic anti-IGF-1R mAb could be useful in treating or preventing endocrinopathic laminitis.
- Published
- 2019
23. 8 Suspected presence of macroprolactin in the plasma of horses and ponies
- Author
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N. Galinelli, N. J. Bamford, M. Erdody, Martin N. Sillence, Pat Harris, and Simon R. Bailey
- Subjects
Equine ,business.industry ,Physiology ,Medicine ,Macroprolactin ,business - Published
- 2021
24. The equine glucose-dependent insulinotropic polypeptide receptor: A potential therapeutic target for insulin dysregulation1
- Author
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Litticia M. Bryant, Murad Hasan Kheder, M.A. de Laat, and Martin N. Sillence
- Subjects
0301 basic medicine ,endocrine system ,medicine.medical_specialty ,medicine.medical_treatment ,Incretin ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Hyperinsulinemia ,Receptor ,business.industry ,Insulin ,Pancreatic islets ,General Medicine ,medicine.disease ,030104 developmental biology ,Postprandial ,Endocrinology ,medicine.anatomical_structure ,Equine metabolic syndrome ,Animal Science and Zoology ,Pancreas ,business ,hormones, hormone substitutes, and hormone antagonists ,Food Science - Abstract
Metabolic disease is a significant problem that causes a range of species-specific comorbidities. Recently, a better understanding of glucose-dependent insulinotropic polypeptide (GIP) biology has led to the suggestion that inhibiting its action may attenuate obesity in several species. In horses, antagonism of GIP may also reduce hyperinsulinemia, which leads to insulin-associated laminitis, a painful comorbidity unique to this species. However, little is known about GIP in horses. The aims of this study were to examine the tissue distribution of equine GIP receptors (eGIPR), to determine whether eGIPR can be blocked using a GIP antagonist not tested previously in horses, and to establish whether there is any association between GIP concentrations and body mass in this species. Archived tissues from healthy horses were used to establish that eGIPR gene expression was strong in pancreas, heart, liver, kidney, and duodenum and absent in gluteal muscle. Pancreatic islets were isolated from fresh horse pancreas using collagenase digestion and layering through a density gradient. Islet viability was confirmed microscopically and by demonstrating that insulin production was stimulated by glucose in a concentration-dependent manner. Insulin release was also shown to be concentration-dependent with GIP up to 0.1µM, and the response to GIP was decreased (P = 0.037) by the antagonist (Pro3)GIP. As for the relationship between body mass and GIP in vivo, postprandial GIP concentrations in archived plasma samples were positively correlated with body condition and cresty neck scores (P < 0.05). Thus, the eGIPR is a potential therapeutic target for insulin dysregulation and obesity in horses.
- Published
- 2017
25. The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies
- Author
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Donald M. Walsh, Martin N. Sillence, Melody A. de Laat, Christopher C. Pollitt, and Danielle M. Fitzgerald
- Subjects
Laminitis ,040301 veterinary sciences ,medicine.medical_treatment ,Incretin ,Gastric Inhibitory Polypeptide ,Horse ,Incretins ,Pasture ,0403 veterinary science ,Random Allocation ,Animal science ,Glucagon-Like Peptide 1 ,Hyperinsulinaemia ,Hyperinsulinism ,Equine metabolic syndrome ,Grazing ,Animals ,Insulin ,Medicine ,Horses ,Fertiliser ,Metabolic Syndrome ,geography ,Cross-Over Studies ,lcsh:Veterinary medicine ,geography.geographical_feature_category ,General Veterinary ,business.industry ,0402 animal and dairy science ,Dietary management ,Insulin dysregulation ,04 agricultural and veterinary sciences ,General Medicine ,Glucose Tolerance Test ,Animal Feed ,040201 dairy & animal science ,Peptide Fragments ,Diet ,Hay ,lcsh:SF600-1100 ,Animal Nutritional Physiological Phenomena ,Horse Diseases ,Queensland ,business ,Research Article - Abstract
Background The oral glucose test (OGT) is a useful tool for diagnosing insulin dysregulation (ID) and is somewhat repeatable in ponies under consistent management. This study aimed to determine whether the insulin and incretin responses to an OGT in ponies differed after short-term access to fertilised pasture, compared to unfertilised pasture, by using a randomised, repeated measures study design. Sixteen mixed-breed ponies were classified as severely insulin-dysregulated (SD; post-prandial insulin ≥80 μIU/mL) or not severely insulin-dysregulated (NSD; post-prandial insulin Results The volume of fertilised pasture was five-fold greater than unfertilised pasture, with % non-structural carbohydrates (NSC) similar between all forages. Consuming fertilised pasture increased (P = 0.018) the serum insulin response to an OGT, compared to grazing unfertilised pasture. A limitation of the study was that pasture intake was unable to be quantified. Insulin responses were greater in SD, compared to NSD, ponies (P Conclusions Whereas some insulin-dysregulated ponies were comparatively resistant to dietary intervention, others showed markedly different OGT responses following subtle changes in their forage-based diet. This implies that mild/early ID might be unmasked by dietary change, and that dietary management is important in these ponies. However, dietary management alone may not be adequate for all cases of ID.
- Published
- 2019
26. An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis
- Author
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Robert J. Spence, Melody A. de Laat, Martin N. Sillence, and Christopher C. Pollitt
- Subjects
Keratinocytes ,Hoof and Claw ,Gene Dosage ,Immunostaining ,Pathology and Laboratory Medicine ,Biochemistry ,Epithelium ,0403 veterinary science ,Pathogenesis ,Basal (phylogenetics) ,Hyperinsulinemia ,Endocrinology ,Epidermal growth factor ,Animal Cells ,Medicine and Health Sciences ,Insulin ,Phosphorylation ,Receptor ,Mammals ,Staining ,0303 health sciences ,Multidisciplinary ,integumentary system ,Eukaryota ,Cell Staining ,04 agricultural and veterinary sciences ,Laminitis ,Basal Cells ,ErbB Receptors ,Vertebrates ,Medicine ,Ponies ,Cellular Types ,Anatomy ,Research Article ,medicine.medical_specialty ,040301 veterinary sciences ,Science ,Equines ,Biology ,Research and Analysis Methods ,Foot Diseases ,03 medical and health sciences ,Signs and Symptoms ,Downregulation and upregulation ,Diagnostic Medicine ,Internal medicine ,Hyperinsulinism ,medicine ,Animals ,Horses ,030304 developmental biology ,Diabetic Endocrinology ,Epidermal Growth Factor ,Organisms ,Biology and Life Sciences ,Epithelial Cells ,Cell Biology ,medicine.disease ,Hormones ,Biological Tissue ,Gene Expression Regulation ,Specimen Preparation and Treatment ,Amniotes ,Horse Diseases - Abstract
Equine laminitis is a disease of the digital epidermal lamellae typified by epidermal cell proliferation and structural collapse. Most commonly the disease is caused by hyperinsulinemia, although the pathogenesis is incompletely understood. Insulin can activate the epidermal growth factor (EGF) system in other species and the present study tested the hypothesis that upregulation of EGF receptor (EGFR) signalling is a key factor in laminitis pathophysiology. First, we examined lamellar tissue from healthy Standardbred horses and those with induced hyperinsulinemia and laminitis for EGFR distribution and quantity using immunostaining and gene expression, respectively. Phosphorylation of EGFR was also quantified. Next, plasma EGF concentrations were compared in healthy and insulin-infused horses, and in healthy and insulin-dysregulated ponies before and after feeding. The EGFR were localised to the secondary epidermal lamellae, with stronger staining in parabasal, rather than basal, cells. No change in EGFR gene expression occurred with laminitis, although the receptor showed some phosphorylation. No difference was seen in EGF concentrations in horses, but in insulin-dysregulated ponies mean, post-prandial EGF concentrations were almost three times higher than in healthy ponies (274 ± 90 vs. 97.4 ± 20.9 pg/mL, P = 0.05). Although the EGFR does not appear to play a major pathogenic role in hyperinsulinemic laminitis, the significance of increased EGF in insulin-dysregulated ponies deserves further investigation.
- Published
- 2019
27. Factors Affecting the Rate and Measurement of Feed Intake for a Cereal-Based Meal in Horses
- Author
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Hunter Doughty, Patricia A. Harris, Melody A. de Laat, Martin N. Sillence, and Tara E. Campbell
- Subjects
Dietary Fiber ,Meal ,Equine ,Biology ,Animal Feed ,Breed ,nervous system diseases ,Diet ,Chaff ,Animal science ,nervous system ,Physical Conditioning, Animal ,mental disorders ,Animals ,Horses ,Edible Grain ,psychological phenomena and processes - Abstract
The rapid intake of high-cereal, low-roughage meals may cause gastrointestinal and behavioral disorders. We investigated some of the factors that can affect the rate of intake (ROI) in four separate studies. Study 1 investigated the effect of chaff length and addition rate on the ROI of oats. The ROI decreased as more chaff was added to the diet, attaining significance (P
- Published
- 2019
28. Incidence and risk factors for recurrence of endocrinopathic laminitis in horses
- Author
-
Melody A. de Laat, James McGree, Dania Birte Reiche, and Martin N. Sillence
- Subjects
Male ,Hoof and Claw ,Standard Article ,030204 cardiovascular system & hematology ,0403 veterinary science ,Cohort Studies ,0302 clinical medicine ,Endocrinology ,Recurrence ,Risk Factors ,Pituitary pars intermedia dysfunction ,Medicine ,Prospective Studies ,Prospective cohort study ,lcsh:Veterinary medicine ,integumentary system ,Incidence (epidemiology) ,Incidence ,04 agricultural and veterinary sciences ,Laminitis ,equine metabolic syndrome ,Standard Articles ,horse ,embryonic structures ,hyperinsulinemia ,Female ,Cohort study ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,animal structures ,040301 veterinary sciences ,Endocrine System Diseases ,Foot Diseases ,03 medical and health sciences ,Internal medicine ,Hyperinsulinism ,Animals ,Horses ,Risk factor ,General Veterinary ,business.industry ,insulin dysregulation ,medicine.disease ,ACTH ,Equine metabolic syndrome ,pituitary pars intermedia dysfunction ,lcsh:SF600-1100 ,Horse Diseases ,Metabolic syndrome ,EQUID ,business - Abstract
Background Endocrinopathic laminitis is common in horses and ponies, but the recurrence rate of the disease is poorly defined. Objectives To determine the incidence of, and risk factors for, the recurrence of endocrinopathic laminitis. Animals Privately owned horses and ponies with acute laminitis (n = 317, of which 276 cases with endocrinopathic laminitis were followed up to study completion). Methods This prospective cohort study collected data on veterinary‐diagnosed cases of acute laminitis for 2 years. Each case was classified on acceptance to the study as endocrinopathic or non‐endocrinopathic using data collected in a questionnaire completed by the animal's veterinarian. Follow‐up data were collected at regular intervals to determine whether the laminitis recurred in the 2‐year period after diagnosis. Results The recurrence rate for endocrinopathic laminitis was 34.1%. The risk of recurrence during the 2‐year study period increased with basal, fasted serum insulin concentration (P ≤ .05), with the probability of recurrence increasing markedly as the insulin concentration increased beyond the normal range (0‐20 μIU/mL) to over the threshold for normal (up to approximately 45 μIU/mL). Being previously diagnosed with laminitis (before the study; P = .05) was also a risk factor for recurrent laminitis. Cases with a higher Obel grade of laminitis were likely (P = .05) to recur sooner. Conclusions and clinical importance Knowing that hyperinsulinemia and being previously diagnosed with laminitis are significant risk factors for recurrence will enable clinicians to proactively address these factors, thereby potentially reducing the risk of recurrence of laminitis.
- Published
- 2018
29. Rapid isolation and detection of erythropoietin in blood plasma by magnetic core gold nanoparticles and portable Raman spectroscopy
- Author
-
Arumugam Sivanesan, Emad L. Izake, Rohan Steel, Roland Agoston, Martin N. Sillence, and William B. Lott
- Subjects
Materials science ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Nanoparticle ,Bioengineering ,Nanotechnology ,02 engineering and technology ,Spectrum Analysis, Raman ,01 natural sciences ,symbols.namesake ,Blood plasma ,Protein purification ,Animals ,Humans ,General Materials Science ,Horses ,Magnetite Nanoparticles ,Erythropoietin ,Chromatography ,010401 analytical chemistry ,Substrate (chemistry) ,Surface-enhanced Raman spectroscopy ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Substance Abuse Detection ,Magnetic core ,Colloidal gold ,Magnets ,symbols ,Molecular Medicine ,Gold ,0210 nano-technology ,Raman spectroscopy ,Antibodies, Immobilized - Abstract
Isolating, purifying, and identifying proteins in complex biological matrices are often difficult, time consuming, and unreliable. Herein we describe a rapid screening technique for proteins in biological matrices that combines selective protein isolation with direct surface enhanced Raman spectroscopy (SERS) detection. Magnetic core gold nanoparticles were synthesized, characterized, and subsequently functionalized with recombinant human erythropoietin (rHuEPO)-specific antibody. The functionalized nanoparticles were used to capture rHuEPO from horse blood plasma within 15 min. The selective binding between the protein and the functionalized nanoparticles was monitored by SERS. The purified protein was then released from the nanoparticles' surface and directly spectroscopically identified on a commercial nanopillar SERS substrate. ELISA independently confirmed the SERS identification and quantified the released rHuEPO. Finally, the direct SERS detection of the extracted protein was successfully demonstrated for in-field screening by a handheld Raman spectrometer within 1 min sample measurement time.The rapid detection of recombinant human erythropoietin (rHuEPO) is important in competitive sports to screen for doping offences. In this article, the authors reported their technique of direct surface enhanced Raman spectroscopy (SERS) detection using magnetic core gold nanoparticles functionalized with recombinant human erythropoietin-specific antibody. The findings should open a new way for future detection of other proteins.
- Published
- 2016
30. The effect of oral and intravenous dextrose on C-peptide secretion in ponies1
- Author
-
J. J. van Haeften, M.A. de Laat, and Martin N. Sillence
- Subjects
0301 basic medicine ,medicine.medical_specialty ,040301 veterinary sciences ,medicine.medical_treatment ,0403 veterinary science ,03 medical and health sciences ,chemistry.chemical_compound ,Internal medicine ,Genetics ,medicine ,Hyperinsulinemia ,C-peptide ,business.industry ,Insulin ,Horse ,04 agricultural and veterinary sciences ,General Medicine ,Laminitis ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Animal Science and Zoology ,Pancreas ,business ,Hyperinsulinism ,Drug metabolism ,Food Science - Abstract
Managing equine hyperinsulinemia is crucial for preventing laminitis, but our understanding of the mechanisms involved in insulin dysregulation in this species is incomplete. C-peptide is co-secreted with insulin but is resistant to hepatic metabolism and can be used to study insulin dysregulation. This study examined C-peptide secretion in serial blood samples collected after oral and i.v. dextrose (0.75 g/kg) administration to 9 ponies (BCS, 7.1 ± 0.5). The ponies were designated as hyperinsulinemic (HI) or normoinsulinemic (NI) responders before the study, using oral glucose tests and fasted glucose-to-insulin ratios, and responses were compared between the 2 groups. C-peptide concentrations increased ( < 0.01) rapidly from fasted levels after both oral and i.v. dextrose, with similar area under the concentration-time curve (AUC) for both tests and a significant correlation with AUC. The AUC was similar in HI and NI ponies after i.v. dextrose, indicating similar pancreatic capacity for both groups. However, for oral dextrose, the AUC and the AUC were markedly higher ( < 0.05) in the HI ponies, indicating a greater secretion rate of these peptides. Slower insulin clearance might have also contributed to the larger AUC in HI ponies, but this hypothesis requires further investigation with specific measures of hepatic insulin clearance.
- Published
- 2016
31. Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation
- Author
-
X M. A. de Laat, Martin N. Sillence, and James McGree
- Subjects
medicine.medical_specialty ,040301 veterinary sciences ,Physiology ,Enteroendocrine Cells ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Incretin ,Biology ,Incretins ,0403 veterinary science ,Insulin resistance ,Hyperinsulinism ,Physiology (medical) ,Internal medicine ,Dietary Carbohydrates ,medicine ,Hyperinsulinemia ,Animals ,Insulin ,Horses ,Glucose tolerance test ,medicine.diagnostic_test ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Glucose Tolerance Test ,medicine.disease ,Animal Feed ,040201 dairy & animal science ,Glucagon-like peptide-1 ,Diet ,Gastrointestinal Tract ,Endocrinology ,Equine metabolic syndrome ,Horse Diseases ,Insulin Resistance - Abstract
Compared with some other species, insulin dysregulation in equids is poorly understood. However, hyperinsulinemia causes laminitis, a significant and often lethal disease affecting the pedal bone/hoof wall attachment site. Until recently, hyperinsulinemia has been considered a counterregulatory response to insulin resistance (IR), but there is growing evidence to support a gastrointestinal etiology. Incretin hormones released from the proximal intestine, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, augment insulin secretion in several species but require investigation in horses. This study investigated peripheral and gut-derived factors impacting insulin secretion by comparing the response to intravenous (iv) and oral d-glucose. Oral and iv tests were performed in 22 ponies previously shown to be insulin dysregulated, of which only 15 were classified as IR (iv test). In a more detailed study, nine different ponies received four treatments: d-glucose orally, d-glucose iv, oats, and commercial grain mix. Insulin, glucose, and incretin concentrations were measured before and after each treatment. All nine ponies showed similar iv responses, but five were markedly hyperresponsive to oral d-glucose and four were not. Insulin responsiveness to oral d-glucose was strongly associated with blood glucose concentrations and oral glucose bioavailability, presumably driven by glucose absorption/distribution, as there was no difference in glucose clearance rates. Insulin was also positively associated with the active amide of GLP-1 following d-glucose and grain. This study has confirmed a functional enteroinsular axis in ponies that likely contributes to insulin dysregulation that may predispose them to laminitis. Moreover, iv tests for IR are not reliable predictors of the oral response to dietary nonstructural carbohydrate.
- Published
- 2016
32. Glucagon-like peptide-1, insulin-like growth factor-1, and adiponectin in insulin-dysregulated ponies: effects of feeding a high nonstructural carbohydrate diet and association with prospective laminitis
- Author
-
M.A. de Laat, Dania Birte Reiche, Alexandra Meier, and Martin N. Sillence
- Subjects
Hoof and Claw ,medicine.medical_specialty ,medicine.medical_treatment ,Foot Diseases ,03 medical and health sciences ,Insulin-like growth factor ,0302 clinical medicine ,Endocrinology ,Food Animals ,Glucagon-Like Peptide 1 ,Internal medicine ,Dietary Carbohydrates ,medicine ,Hyperinsulinemia ,Animals ,Insulin ,Horses ,Insulin-Like Growth Factor I ,Inflammation ,030219 obstetrics & reproductive medicine ,Adiponectin ,business.industry ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Laminitis ,medicine.disease ,040201 dairy & animal science ,Glucagon-like peptide-1 ,Equine metabolic syndrome ,Horse Diseases ,Animal Science and Zoology ,business ,Hormone - Abstract
Endocrinopathic laminitis, related to equine metabolic syndrome and insulin dysregulation, causes marked pain and suffering in horses and represents a substantial cost to the horse industry. This study investigated the effect of feeding a diet high in nonstructural carbohydrates on concentrations of active glucagon-like peptide-1 (aGLP-1), total insulin-like growth factor-1 (IGF-1), and high-molecular-weight (HMW) adiponectin, in insulin-dysregulated ponies. Thirty-seven ponies were challenged with this diet for up to 18 d to induce hyperinsulinemia. Hormone concentrations were measured in selected samples on day 2 of the diet challenge period, over 4 h after feeding. Fourteen of the ponies developed mild laminitis induced by the diet challenge. Insulin and glucose responses to the diet have been reported previously. Feeding increased the concentrations of aGLP-1 (P < 0.05) and HMW adiponectin (P < 0.001), but there was no difference between the laminitic and nonlaminitic groups for either hormone. Concentrations of IGF-1 and insulin were inversely related, with IGF-1 being 32% lower in hyperinsulinemic/laminitic ponies compared with nonlaminitic ponies (P = < 0.05). These results indicate that unlike insulin and possibly IGF-1, concentrations of aGLP-1 and HMW adiponectin do not have a strong association with, or play a major role in, the pathogenesis of equine laminitis.
- Published
- 2020
33. A review of recent developments in the pharmacological prevention and treatment of endocrinopathic laminitis
- Author
-
Melody A. de Laat and Martin N. Sillence
- Subjects
0303 health sciences ,medicine.medical_specialty ,Gabapentin ,040301 veterinary sciences ,business.industry ,Dietary management ,04 agricultural and veterinary sciences ,Laminitis ,Disease ,0403 veterinary science ,03 medical and health sciences ,Equine metabolic syndrome ,medicine ,Pituitary pars intermedia dysfunction ,Animal Science and Zoology ,Intensive care medicine ,business ,Insulin secretion ,Acute pain ,030304 developmental biology ,Food Science ,medicine.drug - Abstract
Despite the prevalence of endocrinopathic laminitis, the pharmacologic options for preventing and treating the disease are severely limited. The present review aims to discuss the spectrum of potential therapeutic agents for the condition, ranging from early experimental compounds to agents nearing registration. There are different pharmacologic targets for, and approaches to, managing laminitis. Reducing hyperinsulinaemia is central to diminishing endocrinopathic laminitis risk, and a detailed understanding of the pathophysiology of insulin dysregulation is necessary to identify pathways that can be targeted to minimise post-prandial insulin secretion and action. This area of research is advancing rapidly, with several exciting prospects, such as sodium-dependent glucose co-transporter-2 inhibitors, on the horizon for the treatment of equine metabolic dysfunction. Drugs that directly target the lamellae and aim to reduce the damage inflicted on the lamellae as part of this condition, are not yet available. Although progress in this area of laminitis therapy is slower, improved understanding of the events that lead to lamellar failure has enabled the investigation of novel drugs that aim to prevent laminitis at the site of the lesion. Finally, a brief review is included of the directions being taken in the management of the chronic and acute pain that accompanies laminitis. Medications for relieving the pain associated with laminitis are currently the most-prescribed drugs for the disease, and range from simple, affordable and thoroughly tested options, such as phenylbutazone, to newer, less-understood applications such as paracetamol and gabapentin. In the future, endocrinopathic laminitis management plans will likely take a multi-faceted approach that still hinge on effective dietary management and exercise, but also include drugs that address foot pathology, pain and underlying endocrine disturbances.
- Published
- 2020
34. Randomised clinical trial on the effect of a single oral administration of l-tryptophan, at three dose rates, on reaction speed, plasma concentration and haemolysis in horses
- Author
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Glenys Noble, Martin N. Sillence, Dagong Zhang, and Xiuhua Li
- Subjects
Male ,Reflex, Startle ,medicine.medical_specialty ,040301 veterinary sciences ,Administration, Oral ,Pharmacology ,Placebo ,Hemolysis ,0403 veterinary science ,Oral administration ,medicine ,Animals ,Horses ,Cross-Over Studies ,Dose-Response Relationship, Drug ,General Veterinary ,Clinical pathology ,business.industry ,Reaction speed ,Tryptophan ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Haemolysis ,040201 dairy & animal science ,Surgery ,Clinical trial ,Antidepressive Agents, Second-Generation ,Animal Science and Zoology ,business ,Dose rate - Abstract
Tryptophan (TRP) is marketed as a calmative for horses despite reservations about its efficacy. The aim of this study was to measure the effect of oral TRP administration on the reaction speed of horses. Sixty mature horses were used in a two stage randomised, blind, cross-over study, receiving a placebo and an oral dose of TRP (30, 60 or 120 mg/kg body weight), before undergoing a reaction speed test. Blood samples were taken up to 96 h after TRP administration, to identify signs of acute haemolytic anaemia. Plasma TRP concentrations were increased (P
- Published
- 2016
35. The oral glucose test predicts laminitis risk in ponies fed a diet high in nonstructural carbohydrates
- Author
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Donald M. Walsh, Christopher C. Pollitt, Martin N. Sillence, Alexandra Meier, Dania Birte Reiche, James McGree, and M.A. de Laat
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Hoof and Claw ,040301 veterinary sciences ,medicine.medical_treatment ,Pituitary Diseases ,Blood sugar ,Biology ,0403 veterinary science ,Foot Diseases ,Endocrinology ,Food Animals ,Adrenocorticotropic Hormone ,Internal medicine ,medicine ,Hyperinsulinemia ,Pituitary pars intermedia dysfunction ,Dietary Carbohydrates ,Animals ,Insulin ,Horses ,Inflammation ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Laminitis ,Glucose Tolerance Test ,medicine.disease ,040201 dairy & animal science ,Basal (medicine) ,Equine metabolic syndrome ,Animal Science and Zoology ,Female ,Horse Diseases ,Metabolic syndrome - Abstract
The aim of this study was to investigate the relationship between laminitis development in ponies and insulin/glucose concentrations in response to the oral glucose test (OGT) and a dietary challenge high in nonstructural carbohydrates (NSCs). After undergoing an OGT (1 g dextrose/kg BW in feed), 37 ponies with 2-h serum insulin concentrations ranging from 22 to 1,133 μIU/mL were subjected to a diet challenge period (DCP), consuming 12 g NSC/kg BW/d for up to 18 d. Insulin and glucose responses were measured on day 2 of the DCP. Clinical laminitis was diagnosed by blinded experts and confirmed radiographically. Basal ACTH levels and clinical signs were assessed to investigate concurrent putative pituitary pars intermedia dysfunction (PPID). The diet induced Obel grade 1 or 2 laminitis in 14 ponies (38%). The ponies that developed laminitis had higher maximum concentrations of blood glucose (P = 0.04) and serum insulin (P = 0.02) in response to the diet. The geometric mean (95% CI) blood glucose concentration for laminitis cases was 14.9 (12.9-17.2) mM, compared to 10.7 (9.2-12.5) mM for ponies who did not develop laminitis. Similarly, the geometric mean (95% CI) for serum insulin was 396 (301-520) μIU/mL for laminitis cases, compared to 216 (148-316) μIU/mL for ponies who did not develop laminitis. Laminitis incidence was likewise associated with insulin concentrations measured during the OGT. Laminitis occurred at frequencies of 0% (0/7) if postdextrose insulin (μIU/mL) was50; 35% (8/23) if insulin was 50 to 195; and 86% (6/7) if insulin was195 μIU/mL. Basal ACTH concentrations were above seasonally accepted reference ranges in 16/37 ponies, and 8 of these animals (50%) developed laminitis. This included all 5 ponies in the study that had clinical signs of PPID (100%). In contrast, hyperinsulinemia and laminitis occurred in only 3/11 ponies (27%) with elevated ACTH concentrations and no clinical signs of PPID (P = 0.009). Thus, laminitis occurrence was associated with higher glucose and insulin responses to both the OGT and challenge diet, and the frequency of laminitis can be predicted based on insulin and glucose hyperresponsiveness to these oral carbohydrate challenges.
- Published
- 2017
36. The cresty neck score is an independent predictor of insulin dysregulation in ponies
- Author
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Stephen T. Anderson, Martin N. Sillence, Melody A. de Laat, and Danielle M. Fitzgerald
- Subjects
Leptin ,Male ,Physiology ,Peptide Hormones ,medicine.medical_treatment ,Biochemistry ,Fats ,0403 veterinary science ,Endocrinology ,Immune Physiology ,Medicine and Health Sciences ,Hyperinsulinemia ,Insulin ,Mammals ,Metabolic Syndrome ,Innate Immune System ,Multidisciplinary ,Eukaryota ,04 agricultural and veterinary sciences ,Prognosis ,Lipids ,Physiological Parameters ,Research Design ,Vertebrates ,Cytokines ,Medicine ,Female ,Adiponectin ,Ponies ,Research Article ,medicine.medical_specialty ,Imaging Techniques ,040301 veterinary sciences ,Science ,Equines ,Immunology ,Research and Analysis Methods ,Adipokines ,Internal medicine ,medicine ,Animals ,Body Weights and Measures ,Obesity ,Horses ,Diabetic Endocrinology ,Anatomy, Veterinary ,business.industry ,Morphometry ,Body Weight ,Hypertriglyceridemia ,Organisms ,0402 animal and dairy science ,Biology and Life Sciences ,Molecular Development ,medicine.disease ,040201 dairy & animal science ,Hormones ,Basal (medicine) ,Equine metabolic syndrome ,Immune System ,Amniotes ,Horse Diseases ,Insulin Resistance ,business ,Biomarkers ,Neck ,Developmental Biology - Abstract
Generalized obesity, regional adiposity, hyperinsulinemia and hypertriglyceridemia are all potential indicators of equine metabolic syndrome (EMS). This study aimed to assess the relationship between morphometric measurements of body condition and metabolic hormone concentrations in ponies, with and without a neck crest or generalised obesity. Twenty-six ponies were assigned a body condition score (BCS) and cresty neck score (CNS). Height, girth, and neck measurements were taken. An oral glucose test (OGT; 0.75g dextrose/kg BW) was performed and blood samples collected prior to and 2 hours post dosing. Basal blood samples were analysed for blood glucose, serum insulin, triglyceride and leptin, and plasma HMW adiponectin concentrations. Post-prandial samples were analysed for serum insulin concentration. The ponies were grouped as having a) a normal to fleshy body status (BCS ≤7 and CNS ≤2; n = 10); b) having a high CNS, but without generalised obesity (BCS ≤7 and CNS ≥3; n = 11), or c) being obese (BCS ≥8 and CNS ≥1; n = 5). Responses to the OGT indicated that both normal and insulin-dysregulated ponies were included in the cohort. Post-prandial serum insulin was positively associated with CNS (P
- Published
- 2019
37. A 'modified Obel' method for the severity scoring of (endocrinopathic) equine laminitis
- Author
-
Melody A. de Laat, Dania Birte Reiche, Daniel Mesa Salas, Ulrich Mengeler, James McGree, Marcella von Salis-Soglio, Donald M. Walsh, Martin N. Sillence, Luke Wells-Smith, Alexandra Meier, Christopher C. Pollitt, and Susanne Droegemueller
- Subjects
Veterinary Medicine ,Laminitis ,Lameness ,040301 veterinary sciences ,Metabolic Sciences ,Concordance ,lcsh:Medicine ,Modified method ,General Biochemistry, Genetics and Molecular Biology ,0403 veterinary science ,Cohen's kappa ,Equine metabolic syndrome ,Insulin ,Medicine ,Horses ,Diagnostics ,business.industry ,General Neuroscience ,lcsh:R ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,General Medicine ,040201 dairy & animal science ,Equine laminitis ,General Agricultural and Biological Sciences ,Nuclear medicine ,business ,Research setting - Abstract
Background Laminitis is a common equine disease characterized by foot pain, and is commonly diagnosed using a five-grade Obel system developed in 1948 using sepsis-related cases. However, endocrinopathic laminitis is now the most common form of the disease and clinical signs may be mild, or spread across two Obel grades. This paper describes a modified method which assigns scores to discreet clinical signs, providing a wider scale suitable for use in a research setting. Methods The “modified Obel” method was developed using an iterative process. First, a prototype method was developed during the detailed observation of 37 ponies undergoing a laminitis induction experiment. The final method was refined and validated using video footage taken during the induction study and from a clinical trial of naturally occurring endocrinopathic laminitis cases. The Obel method was deconstructed and key laminitis signs were evaluated to develop a three-stage, five criteria method that employs a severity scale of 0–12. Veterinarians (n = 28) were recruited to watch and assess 15 video recordings of cases of varying severity, using the Obel and “modified Obel” methods. The inter-observer agreement (reproducibility) was determined using Kendall’s coefficient of concordance (Kendall W) and Krippendorf’s alpha reliability coefficient. A total of 14 veterinarians repeated the exercise 2–4 weeks after their original assessment, to determine intra-observer agreement (repeatability), assessed using a weighted kappa statistic (kw). Agreement between methods was calculated by converting all “modified Obel” scores to Obel grades and calculating the mean and distribution of the differences. Results The “modified Obel” and Obel methods showed excellent and similar inter-observer agreement based on the Kendall W value (0.87, P < 0.001 vs. 0.85, P < 0.001) and Krippendorf’s alpha (95% CI) value (0.83 [0.53–0.90] vs. 0.77 [0.55–0.85]). Based on the kw value, the “modified Obel” method also had substantial repeatability, although slightly less than the Obel method, (0.80 vs. 0.91). Excellent agreement between the methods was found, with the mean difference (95% CI), comparing the Obel grade, with the “modified Obel” score converted to an Obel grade, being −0.12 (−0.19 to −0.06) grades. The Obel and converted “modified Obel” grades were identical 62% of the time (259/420) and a difference of one grade (higher or lower) occurred in 35% of cases (148/420). Conclusion Both methods show excellent agreement, reproducibility and repeatability when used to diagnose endocrinopathic laminitis. The “modified Obel” method is a three-step examination process for severity-scoring of endocrinopathic laminitis, initially proposed for use within a research setting. When using the modified method a diagnosis of laminitis also requires clinical acumen. The allocation of scores for specific clinical signs should be particularly useful in research trials monitoring laminitis recovery.
- Published
- 2019
38. Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse
- Author
-
Martin N. Sillence and Glenys Noble
- Subjects
Meal ,medicine.medical_specialty ,Insulin ,medicine.medical_treatment ,Horse ,General Medicine ,Laminitis ,Biology ,Endocrinology ,Basal (medicine) ,Internal medicine ,Lean body mass ,medicine ,Morning ,Hormone - Abstract
Reasons for performing the study As growth hormone increases lean body mass, it could be a therapy for obese horses. However, growth hormone use induces hyperinsulinaemia in some species, so further investigation is warranted. Objectives To investigate the effects of feeding, exercise and growth hormone therapy on basal insulin concentrations in healthy horses. Study design In vivo experimental study. Methods Blood samples were obtained every 30 min from 12 geldings over 24 h, to establish basal serum insulin concentrations, before they underwent a 3-week exercise programme. Horses were allocated into 2 groups and exercised for another 4 weeks. Group A received daily i.m. injections of recombinant equine growth hormone; 5 mg/day for 5 days, then 12.5 mg/day for 16 days. Blood samples were taken daily before feeding. Insulin vs. time area under curve of Groups A and B were compared using a Student's unpaired t test. Results Horses demonstrated insulin peaks within 2 h of feeding of 577 ± 108.3 pmol/l at 09.30 h and 342.4 ± 75.7 pmol/l at 17.30 h, despite receiving the same meal. The nadir was between midnight and 07.30 h. Exercise had no effect on basal insulin concentrations prior to equine growth hormone administrations. The equine growth hormone injections increased serum insulin concentrations (P = 0.01) within Group A, from 44.4 ± 15.3 pmol/l initially to 320.9 ± 238.2 pmol/l by Day 12. Exogenous growth hormone caused variable hyperinsulinaemia, which was alleviated once equine growth hormone administration ceased. Conclusions Single serum samples taken prior to the morning meal provide basal insulin concentrations. Exercise did not change basal insulin concentrations. However, equine growth hormone injections increased basal insulin concentrations, which were not ameliorated by exercise. Potential relevance This therapy is not recommended to address obesity in insulin-resistant equids.
- Published
- 2013
39. An objective measure of reactive behaviour in horses
- Author
-
Patricia A. Harris, Kathryn L. Blackshaw, Martin N. Sillence, Ann Cowling, and Glenys Noble
- Subjects
Sedation ,Reaction speed ,Horse ,Acepromazine ,Plasma cortisol ,Food Animals ,ACEPROMAZINE MALEATE ,Anesthesia ,Heart rate ,medicine ,Animal Science and Zoology ,Exertion ,medicine.symptom ,Psychology ,medicine.drug - Abstract
Several tests have been devised in an attempt to detect behaviour modification due to training, supplements or diet in horses. These tests rely on subjective observations in combination with physiological measures, such as heart rate (HR) and plasma cortisol concentrations, but these measures do not definitively identify behavioural changes. The aim of the present studies was to develop an objective and relevant measure of horse reactivity. In Study 1, HR responses to auditory stimuli, delivered over 6 days, designed to safely startle six geldings confined to individual stalls was studied to determine if peak HR, unconfounded by physical exertion, was a reliable measure of reactivity. Both mean (±SEM) resting HR (39.5 ± 1.9 bpm) and peak HR (82 ± 5.5 bpm) in response to being startled in all horses were found to be consistent over the 6 days. In Study 2, HR, plasma cortisol concentrations and speed of departure from an enclosure (reaction speed (RS)) in response to a single stimulus of six mares were measured when presented daily over 6 days. Peak HR response (133 ± 4 bpm) was consistent over days for all horses, but RS increased (3.02 ± 0.72 m/s on Day 1 increasing to 4.45 ± 0.53 m/s on Day 6; P = 0.005). There was no effect on plasma cortisol, so this variable was not studied further. In Study 3, using the six geldings from Study 1, the RS test was refined and a different startle stimulus was used each day. Again, there was no change in peak HR (97.2 ± 5.8 bpm) or RS (2.9 ± 0.2 m/s on Day 1 versus 3.0 ± 0.7 m/s on Day 6) over time. In the final study, mild sedation using acepromazine maleate (0.04 mg/kg BW i.v.) decreased peak HR in response to a startle stimulus when the horses (n = 8) were confined to a stall (P = 0.006), but not in an outdoor environment when the RS test was performed. However, RS was reduced by the mild sedation (P = 0.02). In conclusion, RS may be used as a practical and objective test to measure both reactivity and changes in reactivity in horses.
- Published
- 2013
40. A Bayesian approach for estimating detection times in horses: exploring the pharmacokinetics of a urinary acepromazine metabolite
- Author
-
James McGree, Anthony J. Dunstan, Andrew R. McKinney, Fiona Schneiders, Martin N. Sillence, Glenys Noble, and Raymond C. Boston
- Subjects
Male ,Metabolite ,Population ,Urine ,Pharmacology ,chemistry.chemical_compound ,Acepromazine ,Pharmacokinetics ,medicine ,Animals ,Hypnotics and Sedatives ,Horses ,education ,Probability ,Promazine ,Doping in Sports ,Detection limit ,Volume of distribution ,education.field_of_study ,Chromatography ,General Veterinary ,Bayes Theorem ,chemistry ,medicine.drug - Abstract
We describe the population pharmacokinetics of an acepromazine (ACP) metabolite (2-(1-hydroxyethyl)promazine) (HEPS) in horses for the estimation of likely detection times in plasma and urine. ACP (30 mg) was administered to 12 horses, and blood and urine samples were taken at frequent intervals for chemical analysis. A bayesian hierarchical model was fitted to describe concentration-time data and cumulative urine amounts for HEPS. The metabolite HEPS was modelled separately from the parent ACP as the half-life of the parent was considerably less than that of the metabolite. The clearance (Cl/F(PM)) and volume of distribution (V/F(PM)), scaled by the fraction of parent converted to metabolite, were estimated as 769 L/h and 6874 L, respectively. For a typical horse in the study, after receiving 30 mg of ACP, the upper limit of the detection time was 35 h in plasma and 100 h in urine, assuming an arbitrary limit of detection of 1 lg/L and a small (≈0.01) probability of detection. The model derived allowed the probability of detection to be estimated at the population level. This analysis was conducted on data collected from only 12 horses, but we assume that this is representative of the wider population.
- Published
- 2013
41. Persistent digital hyperthermia over a 48h period does not induce laminitis in horses
- Author
-
Melody de Laat, Catherine M. McGowan, Donald M. Walsh, Martin N. Sillence, and Christopher C. Pollitt
- Subjects
Male ,Hyperthermia ,Hoof and Claw ,medicine.medical_specialty ,Hot Temperature ,Hoof ,Vasodilator Agents ,medicine.medical_treatment ,Vasodilation ,Foot Diseases ,Adenosine Triphosphate ,Internal medicine ,Forelimb ,medicine ,Animals ,Horses ,Saline ,Inflammation ,General Veterinary ,business.industry ,Forefoot ,Horse ,Laminitis ,Infusions, Intraosseous ,medicine.disease ,Surgery ,Endocrinology ,Lameness ,Horse Diseases ,Animal Science and Zoology ,business - Abstract
Persistent digital hyperthermia, presumably due to vasodilation, occurs during the developmental and acute stages of insulin-induced laminitis. The objectives of this study were to determine if persistent digital hyperthermia is the principal pathogenic mechanism responsible for the development of laminitis. The potent vasodilator, ATP-MgCl(2) was infused continuously into the distal phalanx of the left forefoot of six Standardbred racehorses for 48 h via intra-osseous infusion to promote persistent digital hyperthermia. The right forefoot was infused with saline solution and acted as an internal control. Clinical signs of lameness at the walk were not detected at 0 h, 24h or 48 h post-infusion. Mean ± SE hoof wall temperatures of the left forefoot (29.4 ± 0.25°C) were higher (P
- Published
- 2012
42. Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses
- Author
-
Melody A. de Laat, Catherine M. McGowan, Martin N. Sillence, and Christopher C. Pollitt
- Subjects
Blood Glucose ,Male ,Glycosuria ,Hoof and Claw ,medicine.medical_specialty ,medicine.medical_treatment ,Drug Administration Schedule ,Foot Diseases ,Pathogenesis ,Insulin resistance ,Hyperinsulinism ,Internal medicine ,medicine ,Animals ,Horses ,Inflammation ,General Veterinary ,business.industry ,Insulin ,Histology ,Laminitis ,medicine.disease ,Glucose ,Endocrinology ,Toxicity ,Horse Diseases ,Animal Science and Zoology ,Histopathology ,Insulin Resistance ,medicine.symptom ,business - Abstract
Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the role of glucose in the pathogenesis of the disease has not been fully investigated. This study aimed to determine the endogenous insulin response to a quantity of glucose equivalent to that administered during a laminitis-inducing, euglycaemic, hyperinsulinaemic clamp, over 48. h in insulin-sensitive Standardbred racehorses. In addition, the study investigated whether glucose infusion, in the absence of exogenous insulin administration, would result in the development of clinical and histopathological evidence of laminitis. Glucose (50% dextrose) was infused intravenously at a rate of 0.68 mL/kg/h for 48. h in treated horses (n = 4) and control horses (n = 3) received a balanced electrolyte solution (0.68 mL/kg/h). Lamellar histology was examined at the conclusion of the experiment. Horses in the treatment group were insulin sensitive (M value 0.039 ± 0.0012. mmol/kg/min and M-to-I ratio (100×) 0.014 ± 0.002) as determined by an approximated hyperglycaemic clamp. Treated horses developed glycosuria, hyperglycaemia (10.7 ± 0.78. mmol/L) and hyperinsulinaemia (208 ± 26.1. μIU/mL), whereas control horses did not. None of the horses became lame as a consequence of the experiment but all of the treated horses developed histopathological evidence of laminitis in at least one foot. Combined with earlier studies, the results showed that laminitis may be induced by either insulin alone or a combination of insulin and glucose, but that it is unlikely to be due to a glucose overload mechanism. Based on the histopathological data, the potential threshold for insulin toxicity (i.e. laminitis) in horses may be at or below a serum concentration of ∼200. μIU/mL.
- Published
- 2012
43. The effect of oral metformin on insulin sensitivity in insulin-resistant ponies
- Author
-
Sharanne Raidal, Patricia A. Harris, Kellie D. Tinworth, Glenys Noble, Martin N. Sillence, and Raymond C. Boston
- Subjects
Blood Glucose ,medicine.medical_specialty ,endocrine system diseases ,medicine.medical_treatment ,Administration, Oral ,Pharmacology ,Placebo ,Internal medicine ,medicine ,Animals ,Hypoglycemic Agents ,Horses ,Dosing ,Cross-Over Studies ,General Veterinary ,business.industry ,Insulin ,nutritional and metabolic diseases ,Insulin sensitivity ,Laminitis ,medicine.disease ,Obesity ,Metformin ,Bioavailability ,Treatment Outcome ,Endocrinology ,Female ,Horse Diseases ,Animal Science and Zoology ,Insulin Resistance ,business ,medicine.drug - Abstract
Metformin may be an effective therapeutic option for insulin-resistant (I-R) horses/ponies because, in humans, it reportedly enhances insulin sensitivity (SI) of peripheral tissues without stimulating insulin secretion. To determine the effect of metformin on insulin and glucose dynamics in I-R ponies, six ponies were studied in a cross-over design by Minimal Model analysis of a frequently-sampled intravenous glucose tolerance test (FSIGT). Metformin was administered at 15 mg/kg bodyweight (BW), orally, twice-daily, for 21 days to the metformin-treated group. The control group received a placebo. A FSIGT was conducted before and after treatment. The Minimal Model of glucose and insulin dynamics rendered indices describing SI, glucose effectiveness (Sg), acute insulin response to glucose (AIRg) and the disposition index (DI). The body condition score (BCS), BW and cresty neck score (CNS) were also assessed. There was no significant change in SI, Sg, AIRg, DI, BW, BCS or CNS in response to metformin, or over time in the control group. There were no measurable benefits of metformin on SI, consistent with recent work showing that the bioavailability of metformin in horses is poor, and chronic dosing may not achieve therapeutic blood concentrations. Alternatively, metformin may only be effective in obese ponies losing weight or with hyperglycaemia.
- Published
- 2012
44. Advanced glycation endproducts in horses with insulin-induced laminitis
- Author
-
M.T. Kyaw-Tanner, Catherine M. McGowan, Christopher C. Pollitt, Martin N. Sillence, and M.A. de Laat
- Subjects
Glycation End Products, Advanced ,Hoof and Claw ,medicine.medical_specialty ,medicine.medical_treatment ,Molecular Sequence Data ,Receptor for Advanced Glycation End Products ,Immunology ,Biology ,Carbohydrate metabolism ,medicine.disease_cause ,Polymerase Chain Reaction ,RAGE (receptor) ,Foot Diseases ,Pathogenesis ,Downregulation and upregulation ,Internal medicine ,medicine ,Animals ,Horses ,Cloning, Molecular ,Receptors, Immunologic ,Glucose Transporter Type 4 ,Base Sequence ,General Veterinary ,Insulin ,Glucose transporter ,Laminitis ,Oxidative Stress ,Endocrinology ,Excitatory Amino Acid Transporter 2 ,Gene Expression Regulation ,Horse Diseases ,Lipid Peroxidation ,Reactive Oxygen Species ,Oxidative stress - Abstract
Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of cancer, inflammatory conditions and diabetic complications. An interaction of AGEs with their receptor (RAGE) results in increased release of pro-inflammatory cytokines and reactive oxygen species (ROS), causing damage to susceptible tissues. Laminitis, a debilitating foot condition of horses, occurs in association with endocrine dysfunction and the potential involvement of AGE and RAGE in the pathogenesis of the disease has not been previously investigated. Glucose transport in lamellar tissue is thought to be largely insulin-independent (GLUT-1), which may make the lamellae susceptible to protein glycosylation and oxidative stress during periods of increased glucose metabolism. Archived lamellar tissue from horses with insulin-induced laminitis (n=4), normal control horses (n=4) and horses in the developmental stages (6 h, 12 h and 24 h) of the disease (n=12) was assessed for AGE accumulation and the presence of oxidative protein damage and cellular lipid peroxidation. The equine-specific RAGE gene was identified in lamellar tissue, sequenced and is now available on GenBank. Lamellar glucose transporter (GLUT-1 and GLUT-4) gene expression was assessed quantitatively with qRT-PCR in laminitic and control horses and horses in the mid-developmental time-point (24 h) of the disease. Significant AGE accumulation had occurred by the onset of insulin-induced laminitis (48 h) but not at earlier time-points, or in control horses. Evidence of oxidative stress was not found in any group. The equine-specific RAGE gene was not expressed differently in treated and control animals, nor was the insulin-dependent glucose transporter GLUT-4. However, the glucose transporter GLUT-1 was increased in lamellar tissue in the developmental stages of insulin-induced laminitis compared to control horses and the insulin-independent nature of the lamellae may facilitate AGE formation. However, due to the lack of AGE accumulation during disease development and a failure to detect an increase in ROS or upregulation of RAGE, it appears unlikely that oxidative stress and protein glycosylation play a central role in the pathogenesis of acute, insulin-induced laminitis.
- Published
- 2012
45. The repeatability of an oral glucose test in ponies
- Author
-
M.A. de Laat and Martin N. Sillence
- Subjects
Blood Glucose ,040301 veterinary sciences ,medicine.medical_treatment ,0403 veterinary science ,Eating ,Animal science ,medicine ,Animals ,Insulin ,Palatability ,Horses ,Glucose tolerance test ,Bran ,medicine.diagnostic_test ,business.industry ,0402 animal and dairy science ,Repeated measures design ,Reproducibility of Results ,04 agricultural and veterinary sciences ,General Medicine ,Repeatability ,Carbohydrate ,Glucose Tolerance Test ,040201 dairy & animal science ,Animal Feed ,Equine metabolic syndrome ,business - Abstract
Reasons for performing study - Insulin dysregulation can be difficult to diagnose from basal insulin and glucose concentrations, so a field-based oral glucose test (OGT) is preferred. However, the repeatability of this test has not been reported. Objectives - To determine the repeatability of an in-feed OGT in ponies and examine some factors affecting the palatability of the test meal. Study design - A repeated measures, longitudinal study. Methods - An in-feed OGT was performed at 08.00 h on 3 consecutive occasions under controlled conditions in 8 mixed breed ponies. d-glucose (0.75 g/kg bwt) was dissolved in water and combined with wheat bran and lucerne chaff. Blood samples were taken before and 90, 120, 180 min and 24 h after d-glucose. The repeatability of the test was analysed with repeated measures ANOVA. Insulin and glucose responses to d-glucose were also compared to an equivalent dose of dietary carbohydrate provided with a commercial grain mixture. Results - The overall insulin responses to the OGTs did not differ between tests. Individual insulin responses were more variable (P
- Published
- 2015
46. The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity
- Author
-
M.A. de Laat, Alireza Nourian, M.T. Kyaw-Tanner, Catherine M. McGowan, Martin N. Sillence, and Christopher C. Pollitt
- Subjects
Hoof and Claw ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Gene Expression ,Matrix metalloproteinase ,Biology ,Systemic inflammation ,Foot Diseases ,Pathogenesis ,Extracellular matrix ,Downregulation and upregulation ,Hyperinsulinism ,Internal medicine ,Matrix Metalloproteinase 14 ,medicine ,Animals ,Horses ,RNA, Messenger ,DNA Primers ,Tissue Inhibitor of Metalloproteinase-3 ,Base Sequence ,General Veterinary ,Reverse Transcriptase Polymerase Chain Reaction ,ADAMTS ,Insulin ,Laminitis ,Matrix Metalloproteinases ,ADAM Proteins ,Endocrinology ,Matrix Metalloproteinase 9 ,Acute Disease ,ADAMTS4 Protein ,Matrix Metalloproteinase 2 ,Horse Diseases ,medicine.symptom ,Procollagen N-Endopeptidase - Abstract
Metalloproteinases have been implicated in the pathogenesis of equine laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n = 4) and horses that developed laminitis after 48 h of induced hyperinsulinaemia (n = 4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6 h (n = 4), 12 h (n = 4), 24 h (n = 4) and 48 h (n = 4), and in normal control horses (n = 4). The only change in gene expression observed was an upregulation of MMP-9 (p < 0.05) in horses that developed insulin-induced laminitis (48 h). Zymographical analysis showed an increase (p < 0.05) in pro MMP-9 during the acute phase of laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in laminitis is uncertain as it appears to be present largely in the inactive form.
- Published
- 2011
47. Glucose transport in the equine hoof
- Author
-
J. D. Curlewis, K. E. Asplin, Catherine M. McGowan, Christopher C. Pollitt, and Martin N. Sillence
- Subjects
medicine.medical_specialty ,Insulin ,medicine.medical_treatment ,Glucose uptake ,Glucose transporter ,General Medicine ,Laminitis ,Biology ,Carbohydrate metabolism ,medicine.disease ,Endocrinology ,Insulin resistance ,Internal medicine ,medicine ,biology.protein ,GLUT1 ,GLUT4 - Abstract
Reasons for performing study: Several conditions associated with laminitis in horses are also associated with insulin resistance, which represents the failure of glucose uptake via the insulin-responsive glucose transport proteins in certain tissues. Glucose starvation is a possible mechanism of laminitis, but glucose uptake mechanisms in the hoof are not well understood. Objectives: To determine whether glucose uptake in equine lamellae is dependent on insulin, to characterise the glucose transport mechanism in lamellae from healthy horses and ponies, and to compare this with ponies with laminitis. Methods: Study 1 investigated the effects of insulin (300μU/ml; acute and 24h) and various concentrations of glucose up to 24mmol/l, on 2-deoxy-D-[2,6-H]glucose uptake in hoof lamellar explants in vitro. Study 2 measured the mRNA expression of GLUT1 and GLUT4 transport proteins by PCR analysis in coronary band and lamellar tissue from healthy horses and ponies, ponies with insulin-induced laminitis, and ponies suffering from chronic laminitis as a result of equine Cushing's syndrome. Results: Glucose uptake was not affected by insulin. Furthermore, the relationship between glucose concentration and glucose uptake was consistent with an insulin-independent glucose transport system. GLUT1 mRNA expression was strong in brain, coronary band and lamellar tissue, but was weak in skeletal muscle. Expression of GLUT4 mRNA was strong in skeletal muscle, but was either absent or barely detectable in coronary band and lamellar tissue. Conclusions: The results do not support a glucose deprivation model for laminitis, in which glucose uptake in the hoof is impaired by reduced insulin sensitivity. Hoof lamellae rely on a GLUT1-mediated glucose transport system, and it is unlikely that GLUT4 proteins play a substantial role in this tissue. Potential relevance: Laminitis associated with insulin resistance is unlikely to be due to impaired glucose uptake and subsequent glucose deprivation in lamellae.
- Published
- 2011
48. Pharmacokinetics of metformin after enteral administration in insulin-resistant ponies
- Author
-
Kellie D. Tinworth, Scott Edwards, L. Peter Hackett, Martin N. Sillence, Glenys Noble, and Patricia A. Harris
- Subjects
medicine.medical_specialty ,Administration, Oral ,Enteral administration ,Drug Administration Schedule ,Pharmacokinetics ,Oral administration ,Internal medicine ,Blood plasma ,medicine ,Animals ,Hypoglycemic Agents ,Horses ,General Veterinary ,business.industry ,Area under the curve ,General Medicine ,Metformin ,Bioavailability ,Endocrinology ,Equine metabolic syndrome ,Area Under Curve ,Horse Diseases ,Insulin Resistance ,business ,Half-Life ,medicine.drug - Abstract
Objective—To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies Animals—8 IR ponies Procedures—Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 days, and blood samples were obtained every 2 days. Plasma concentration at steady state (Css) was determined. Results—Mean ± SD elimination half-life (t1/2) of metformin was 11.7 ± 5.2 hours, maxima plasma concentration was 748 ± 269 ng/mL at 54 ± 32 minutes, mean area under the curve was 355 ± 92μg•h/mL, and apparent clearance was 90.6 ± 28.1 mL/min/kg. The Css was 122 ± 22 ng/mL. Conclusions and Clinical Relevance—Metformin reportedly enhances insulin sensitivity of peripheral tissues without stimulating insulin secretion, but bioavailability in horses is low. The t1/2 of metformin in IR ponies was similar to that in humans. Actual clearance of metformin adjusted for bioavailability in IR ponies was similar to that in humans; however, during chronic oral administration at dosages reported in efficacy studies, the Css of metformin was less than values associated with therapeutic efficacy in humans The apparent lack of long-term efficacy of metformin in horses is likely attributable to low bioavailability, rather than to rapid clearance. (Am J Vet Res 2010;71:1201-1206)
- Published
- 2010
49. Histopathology of insulin-induced laminitis in ponies
- Author
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Martin N. Sillence, Catherine M. McGowan, K. E. Asplin, Christopher C. Pollitt, and Janet C. Patterson-Kane
- Subjects
Basement membrane ,medicine.medical_specialty ,Pathology ,integumentary system ,Horse ,Histology ,General Medicine ,Laminitis ,Biology ,medicine.anatomical_structure ,Dermis ,medicine ,Histopathology ,Calprotectin ,Immunostaining - Abstract
Reasons for performing study: Ponies with laminitis associatedwith insulin resistance and hyperinsulinaemia lack systemicand/or intestinal inflammatory signs, suggesting a differentpathogenesis potentially reflected in differing histopathology.Objectives: To describe the histological appearance andquantify morphological changes in primary and secondaryepidermal lamellae (PEL and SEL) of laminitis lesions fromponies with insulin-induced laminitis.Methods: Equine hoof lamellar tissue was obtained from 4control ponies and 5 ponies with laminitis induced followinginfusion of insulin (1036 ± 55 mU/ml) while maintainingeuglycaemia for 55.4 ± 5.5 h. Sections from all 4 hooves werestained and examined by a veterinary pathologist.Measurements of lamellar length (PEL and SEL) were madein mid-dorsal sections of the right forefeet by 2 blindedobservers. Immunolabelling for calprotectin was performedusing a monoclonal antibody.Results: No lesions were detected in normal ponies. Lesionsdetected in ponies with laminitis were variable in severitybetween ponies.Within ponies, SEL lesions were more severealong the axial region of PEL. Lesions included swelling,disorganisation and abnormal keratinisation of epidermalcells, increased mitotic activity and apoptosis. Separation ofbasement membranes wasminimal. Immunostaining revealedinflammatory cells within the lamellar dermis. SEL weresignificantly elongated in laminitic hooves relative to controls,with the greatest elongation in those attached to abaxial andmiddle regions of PEL.Conclusions: Laminitis induced by prolonged infusion of insulinlacked widespread basement membrane disintegration, andincreases in epidermal cellular proliferation at axial aspectswere marked for this acute stage of disease.Potential releVance: Defining equine laminitis entirely interms of separation of the basement membrane may not beappropriate for laminitis associated with hyperinsulinaemia.
- Published
- 2010
50. Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation
- Author
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Murad Hasan Kheder, Melody A. de Laat, Martin N. Sillence, and Christopher C. Pollitt
- Subjects
0301 basic medicine ,Physiology ,Glucose uptake ,medicine.medical_treatment ,lcsh:Medicine ,Social Sciences ,Pharmacology ,Biochemistry ,Receptors, G-Protein-Coupled ,0403 veterinary science ,chemistry.chemical_compound ,Endocrinology ,Intestine, Small ,Insulin Secretion ,Benzene Derivatives ,Medicine and Health Sciences ,Hyperinsulinemia ,Insulin ,Psychology ,Medicine ,lcsh:Science ,Lactisole ,Mammals ,Multidisciplinary ,biology ,Organic Compounds ,Monosaccharides ,Eukaryota ,04 agricultural and veterinary sciences ,Laminitis ,Effective dose (pharmacology) ,Blood Sugar ,Body Fluids ,3. Good health ,Chemistry ,Blood ,Taste ,Physical Sciences ,Vertebrates ,Sensory Perception ,Gymnema sylvestre ,Ponies ,Anatomy ,Research Article ,040301 veterinary sciences ,Equines ,Carbohydrates ,Blood sugar ,03 medical and health sciences ,Hyperinsulinism ,Animals ,Horses ,Diabetic Endocrinology ,Endocrine Physiology ,business.industry ,lcsh:R ,Organic Chemistry ,Chemical Compounds ,Organisms ,Biology and Life Sciences ,biology.organism_classification ,medicine.disease ,Hormones ,Glucose ,030104 developmental biology ,Intestinal Absorption ,chemistry ,Amniotes ,lcsh:Q ,Horse Diseases ,business ,Neuroscience - Abstract
Hyperinsulinemia is a major risk factor for equine laminitis, a debilitating and painful foot condition. Sweet taste receptor (T1R2/3) inhibitors have been used to reduce the insulin and glucose responses to oral carbohydrates in other species. However, their effect in horses has not been investigated. It would be useful to be able to attenuate the large post-prandial insulin response that typically occurs when a carbohydrate-rich meal is fed to insulin-dysregulated horses. Here we have determined the efficacy of two T1R2/3 inhibitors, lactisole and Gymnema sylvestre, for reducing glucose uptake by the equine small intestine in vitro; and post-prandial insulin secretion in ponies in vivo, following a carbohydrate-based meal. We used gas chromatography-mass spectrometry to measure 2-deoxyglucose uptake by explants of small intestine, in the presence and absence of the T1R2/3 inhibitors. Lactisole and G sylvestre reduced 2-deoxyglucose uptake by the intestinal explants by 63% (P = 0.032) and 73% (P = 0.047), respectively, compared to control samples. The study in vivo investigated the effect of the inhibitors on the blood glucose and serum insulin responses to a meal containing D-glucose. Three doses of each inhibitor were tested using a Latin square design, and each dose was compared to a meal with no inhibitor added. Lactisole had no effect on glucose and insulin concentrations, whereas G sylvestre was partially effective at reducing post-prandial blood glucose (by ~10%) and serum insulin concentrations (~25%) in seven ponies, with a most effective dose of 10 mg/kg bodyweight. These data provide preliminary support that T1R2/3 inhibitors may be a useful therapeutic strategy for the management of equine insulin dysregulation and the prevention of laminitis. However, further optimisation of the dose and delivery method for these compounds is required, as well as a direct investigation of their activity on the equine sweet taste receptor.
- Published
- 2018
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