Search

We hypothesized a differential activation of the anabolic signaling proteins protein kinase B (PKB) and p70 S6 kinase ([p70.sup.S6K]) and subsequent differential stimulation of human muscle protein synthesis (MPS) after dynamic shortening or lengthening exercise. Eight healthy men [25 [+ or -] 5 yr, BMI 26 [+ or -] 3 kg/[m.sup.-2] (means [+ or -] SD)] were studied before and alter 12 min of repeated stepping up to knee height, and down again, while carrying 25% of their body weight, i.e., shortening exercise with the ''up' leg and lengthening exercise with contralateral 'down' leg. Quadriceps biopsies were taken before and 3, 6, and 24 h after exercise. After exercise, over 2 h before the biopsies, the subjects ingested 500 ml of water containing 45 g of essential amino acids and 135 g of sucrose. Rates of muscle protein synthesis were determined via incorporation over time of [1-[sup.13]C]leucine ([less than or equal to]6 h after exercise) or [1-[sup.13]C]valine (21-24 h after exercise) and phosphorylation of signaling proteins by Western analysis. PKB and [p70.sup.S6K] phosphorylation increased ~3-fold after 3 h and remained elevated at 6 and 24 h. After exercise, rates of myofibrillar and sarcoplasmic protein synthesis were unchanged over the period including exercise and 3 h of recovery but had increased significantly at 6 (~3.0- and 2.4-fold, respectively) and 24 h (~3.2- and 2.0-fold, respectively), independently of the mode of exercise. Short-term dynamic exercise in either shortening or lengthening mode increases MPS at least as much as resistance exercise and is associated with long-term activation of PKB and [p70.sup.S6K]. exercise-induced anabolism; myofibrillar, sarcoplasmic, and collagen synthesis

Objective: Pancreatic neuroendocrine tumours (panNETs) arise sporadically or as part of a genetic predisposition syndrome. CT/MRI, endoscopic ultrasonography and functional imaging using Octreoscan localise and stage disease. This study aimed to evaluate the complementary role of 68Gallium (68Ga)-DOTA PET/CT in managing patients with panNETs. Design: A retrospective study conducted across three tertiary UK NET referral centres. Methods: Demographic, clinical, biochemical, cross-sectional and functional imaging data were collected from patients who had undergone a 68Ga-DOTA PET/CT scan for a suspected panNET. Results: We collected data for 183 patients (97 male): median (SD) age 63 (14.9) years, 89.1 vs. 9.3% (n=163 vs. 17) alive vs. dead (3 data missing), 141 sporadic vs. 42 familial (MEN1, n=36; 85.7%) panNETs. Non-functional vs. functional tumours comprised 73.2 vs. 21.3% (n=134 vs. 39) (10 missing). Histological confirmation was available in 89% of individuals (n=163) but tumour grading (Ki67 classiifcation) was technically possible only in a smaller cohort (n=143): grade 1, 50.3% (n=72); grade 2, 46.2% (n=66) and grade 3, 3.5% (n=5) (40 histopathological classification either not technically feasible or biopsy not perfomed). 60.1% (n=110) were localised, 14.2% (n=26) locally advanced and 23.5% (n=43) metastatic (4 missing). 224 68Ga-DOTA PET/CT scans were performed in total for: diagnosis/staging 40% (n=88), post-operative assessment/clinical surveillance 53% (n=117) and consideration of peptide receptor radionuclide therapy (PRRT) 8% (n=17) (2 missing). PET/CT results confirmed other imaging findings (53%), identified new disease sites (28.5%) and excluded suspected disease (5%). Overall, 68Ga-DOTA PET/CT imaging findings provided additional information in 119 (54%) patients and influenced management in 85 (39%) cases. Conclusion: 68Ga-DOTA PET/CT imaging more accurately stages and guides treatment in patients with sporadic/familial panNETs with newly diagnosed/recurrent disease. [ABSTRACT FROM AUTHOR]

Abstract Background Recently, metabolic syndrome (MS) has gained attention in human metabolic medicine given its associations with development of type 2 diabetes mellitus and cardiovascular disease. Canine obesity is associated with the development of insulin resistance, dyslipidaemia, and mild hypertension, but the authors are not aware of any existing studies examining the existence or prevalence of MS in obese dogs. Thirty-five obese dogs were assessed before and after weight loss (median percentage loss 29%, range 10-44%). The diagnostic criteria of the International Diabetes Federation were modified in order to define canine obesity-related metabolic dysfunction (ORMD), which included a measure of adiposity (using a 9-point body condition score [BCS]), systolic blood pressure, fasting plasma cholesterol, plasma triglyceride, and fasting plasma glucose. By way of comparison, total body fat mass was measured by dual-energy X-ray absorptiometry, whilst total adiponectin, fasting insulin, and high-sensitivity C-reactive protein (hsCRP) were measured using validated assays. Results Systolic blood pressure (P = 0.008), cholesterol (P = 0.003), triglyceride (P = 0.018), and fasting insulin (P P = 0.001). However, hsCRP did not change with weight loss. Prior to weight loss, 7 dogs were defined as having ORMD, and there was no difference in total fat mass between these dogs and those who did not meet the criteria for ORMD. However, plasma adiponectin concentration was less (P = 0.031), and plasma insulin concentration was greater (P = 0.030) in ORMD dogs. Conclusions In this study, approximately 20% of obese dogs suffer from ORMD, and this is characterized by hypoadiponectinaemia and hyperinsulinaemia. These studies can form the basis of further investigations to determine path genetic mechanisms and the health significance for dogs, in terms of disease associations and outcomes of weight loss.

Abstract Introduction Idiopathic intracranial hypertension can rarely be associated with an underlying endocrine disorder such as Cushing's syndrome, hyperthyroidism, or with administration of thyroxine or growth hormone. Though cases of idiopathic intracranial hypertension associated with Addison's disease in children have been reported, there is only one documented case report of this association in adults. We describe a case of an acute adrenal insufficiency precipitated by idiopathic intracranial hypertension in a Caucasian female. Case presentation A 24-year-old Caucasian woman was acutely unwell with a background of several months of generalised fatigue and intermittent headaches. She had unremarkable neurological and systemic examination with a normal computerised tomography and magnetic resonance imaging of the brain. Normal cerebrospinal fluid but increased opening pressure at lumbar puncture suggested intracranial hypertension. A flat short synacthen test and raised level of adrenocorticotrophic hormone were consistent with primary adrenal failure. Conclusion Addison's disease can remain unrecognised until precipitated by acute stress. This case suggests that idiopathic intracranial hypertension can rarely be associated with Addison's disease and present as an acute illness. Idiopathic intracranial hypertension is possibly related to an increase in the levels of arginine vasopressin peptide in serum and cerebrospinal fluid secondary to a glucocorticoid deficient state.

To systematically review the current literature investigating associations between zinc-alpha2-glycoprotein (ZAG) and dysglycaemia (including type 2 diabetes (T2DM), poly-cystic-ovary syndrome (PCOS), pre-diabetes or insulin resistance). This included relationships between ZAG and continuous measures of insulin and glucose. Additionally, we performed a meta-analysis to estimate the extent that ZAG differs between individuals with or without dysglycaemia; whilst examining the potential influence of adiposity. A systematic search was performed on four databases for studies on circulating ZAG concentrations in adult human populations, comparing healthy controls to individuals with dysglycaemia. Key characteristics, including the mean ZAG concentrations (mg∙L−1), and any correlational statistics between ZAG and continuous measures of glucose, glycated haemoglobin (HbA1c) or insulin were extracted. Meta-analyses were performed to compare metabolically healthy controls to cases, and on studies that compared controls and cases considered overweight or obese (body mass index (BMI) ≥25 kg.m2). 1575 papers were identified and 14 studies (16 cohorts) were considered eligible for inclusion. Circulating ZAG was lower in individuals with dysglycaemia compared to metabolically healthy controls (−4.14 [−8.17, −0.11] mg.L−1; I2 = 98.5%; p < 0.001). When using data from only studies with overweight or obese groups with or without dysglycaemia (three studies (four cohorts); pooled n = 332), the difference in circulating ZAG was no longer significant (−0.30 [−3.67, 3.07] mg. L−1; I2 = 28.0%; p = 0.225). These data suggest that ZAG may be implicated in dysglycaemia, although there was significant heterogeneity across different studies and the mediating effect of adiposity cannot be excluded. Therefore, more research is needed before robust conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Cardiac autonomic neuropathy (CAN) is a major complication of type 1 and type 2 diabetes mellitus (T1DM and T2DM). The increased morbidity, cardiovascular and all-cause mortality associated with CAN is established from numerous epidemiological studies. However, CAN is increasingly recognised in people with prediabetes (pre-DM) and the metabolic syndrome (MetS) with a reported prevalence up to 11% and 24% respectively. CAN is associated with components of MetS including hypertension and obesity, predating hyperglycaemia. The aetiology of CAN is multifactorial and there is a reciprocal relationship with insulin resistance and MetS. Obstructive sleep apnoea (OSA) is also associated with CAN possibly through MetS and an independent mechanism. An estimated global prevalence of the impaired glucose tolerance (IGT) form of pre-DM of 587 million people by 2045 means CAN will become a major clinical problem. CAN is independently associated with silent myocardial ischaemia, major cardiovascular events, myocardial dysfunction and cardiovascular mortality. Screening for CAN in pre-DM using risk scores with analysis of heart rate variability (HRV) or Sudoscan is important to allow earlier treatment at a reversible stage. The link between obesity and CAN highlights the therapeutic potential of lifestyle interventions including diet and physical activity to reverse MetS and prevent CAN. Weight loss achieved using these dietary and exercise lifestyle interventions improves the sympathetic and parasympathetic HRV indices of cardiac autonomic function. Further research is needed to identify high-risk populations of people with pre-DM or obesity that might benefit from targeted pharmacotherapy including metformin, sodium/glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) analogues. Bariatric surgery also improves HRV through weight loss which might also prevent CAN in severe obesity. This article reviews the literature on CAN in obesity, pre-DM and MetS, to help determine a rationale for screening, early intervention treatment and formulate future research questions in this highly prevalent condition. [ABSTRACT FROM AUTHOR]