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Abstract Background Therapeutic interventions for diabetes are most effective when administered in the newly onset phase, yet determining the exact onset moment can be elusive in practice. Spontaneous autoimmune diabetes among NOD mice appears randomly between 12 and 32 weeks of age with an incidence range from 60 to 90%. Furthermore, the disease often progresses rapidly to severe diabetes within days, resulting in a very short window of newly onset phase, that poses significant challenge in early diagnosis. Conventionally, extensive blood glucose (BG) testing is typically required on large cohorts throughout several months to conduct prospective survey. We incorporated ultrasensitive urine glucose (UG) testing into an ordinary BG survey process, initially aiming to elucidate the lag period required for excessive glucose leaking from blood to urine during diabetes progression in the mouse model. Results The observations unexpectedly revealed that small amounts of glucose detected in the urine often coincide with, sometimes even a couple days prior than elevated BG is diagnosed. Accordingly, we conducted the UG-based survey protocol in another cohort that was validated to accurately identified every individual near onset, who could then be confirmed by following few BG tests to fulfill the consecutive BG + criteria. This approach required fewer than 95 BG tests, compared to over 700 tests with traditional BG survey, to diagnose all the 37–38 diabetic mice out of total 60. The average BG level at diagnosis was slightly below 350 mg/dl, lower than the approximately 400 mg/dl observed with conventional BG monitoring. Conclusions We demonstrated a near perfect correlation between BG + and ultrasensitive UG + results in prospective survey with no lag period detected under twice weekly of testing frequency. This led to the refined protocol based on surveying with noninvasive UG testing, allowing for the early identification of newly onset diabetic mice with only a few BG tests required per mouse. This protocol significantly reduces the need for extensive blood sampling, lancet usage, labor, and animal distress, aligning with the 3Rs principle. It presents a convenient, accurate, and animal-friendly alternative for early diabetes diagnosis, facilitating research on diagnosis, pathogenesis, prevention, and treatment.

Background: Therapeutic interventions for diabetes are most effective when administered in the newly onset phase, yet determining the exact onset moment can be elusive in practice. Spontaneous autoimmune diabetes among NOD mice appears randomly between 12 and 32 weeks of age with an incidence range from 60 to 90%. Furthermore, the disease often progresses rapidly to severe diabetes within days, resulting in a very short window of newly onset phase, that poses significant challenge in early diagnosis. Conventionally, extensive blood glucose (BG) testing is typically required on large cohorts throughout several months to conduct prospective survey. We incorporated ultrasensitive urine glucose (UG) testing into an ordinary BG survey process, initially aiming to elucidate the lag period required for excessive glucose leaking from blood to urine during diabetes progression in the mouse model. Results: The observations unexpectedly revealed that small amounts of glucose detected in the urine often coincide with, sometimes even a couple days prior than elevated BG is diagnosed. Accordingly, we conducted the UG-based survey protocol in another cohort that was validated to accurately identified every individual near onset, who could then be confirmed by following few BG tests to fulfill the consecutive BG + criteria. This approach required fewer than 95 BG tests, compared to over 700 tests with traditional BG survey, to diagnose all the 37–38 diabetic mice out of total 60. The average BG level at diagnosis was slightly below 350 mg/dl, lower than the approximately 400 mg/dl observed with conventional BG monitoring. Conclusions: We demonstrated a near perfect correlation between BG + and ultrasensitive UG + results in prospective survey with no lag period detected under twice weekly of testing frequency. This led to the refined protocol based on surveying with noninvasive UG testing, allowing for the early identification of newly onset diabetic mice with only a few BG tests required per mouse. This protocol significantly reduces the need for extensive blood sampling, lancet usage, labor, and animal distress, aligning with the 3Rs principle. It presents a convenient, accurate, and animal-friendly alternative for early diabetes diagnosis, facilitating research on diagnosis, pathogenesis, prevention, and treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Canine diabetes mellitus has mostly been studied in northern European, Australian and American populations, whereas other regions have received less attention. Objectives We evaluated the epidemiological, clinical and histopathological features of diabetic dogs in Gran Canaria, Spain. Methods Prevalence and incidence were estimated. Clinical features were analysed, and serum and genomic DNA were obtained. Dogs with presumed idiopathic or immune‐mediated diabetes, were DLA‐typed and antibodies against GAD65 and IA‐2 were assessed. Pancreases from ten diabetic dogs were examined and compared with pancreases from non‐diabetic dogs. Results and conclusions Twenty‐nine diabetic dogs were identified in a population of 5,213 (prevalence: 0.56%; incidence: 0.37%). Most were female (79%) and sexually intact (87% of females, 83% of males). Diabetes secondary to dioestrus (55.2%) and insulin‐deficient diabetes (20.7%) were the most frequent types. Antibodies against GAD65 and IA‐2 were identified in two out of five cases and DLA‐genotyping revealed novel haplotypes. Breed distribution differed between diabetic and non‐diabetic dogs. Reduced number of pancreatic islets and β‐cell mass were observed, with vacuolation of islet cells and ductal epithelium. In this population, where neutering is not standard practice, diabetes secondary to dioestrus is the most frequent diabetes subtype. Genetic susceptibility also differed from previous studies. These results support the heterogeneous pathogenesis of canine diabetes.

Background: Canine diabetes mellitus has mostly been studied in northern European, Australian and American populations, whereas other regions have received less attention. Objectives: We evaluated the epidemiological, clinical and histopathological features of diabetic dogs in Gran Canaria, Spain. Methods: Prevalence and incidence were estimated. Clinical features were analysed, and serum and genomic DNA were obtained. Dogs with presumed idiopathic or immune‐mediated diabetes, were DLA‐typed and antibodies against GAD65 and IA‐2 were assessed. Pancreases from ten diabetic dogs were examined and compared with pancreases from non‐diabetic dogs. Results and conclusions: Twenty‐nine diabetic dogs were identified in a population of 5,213 (prevalence: 0.56%; incidence: 0.37%). Most were female (79%) and sexually intact (87% of females, 83% of males). Diabetes secondary to dioestrus (55.2%) and insulin‐deficient diabetes (20.7%) were the most frequent types. Antibodies against GAD65 and IA‐2 were identified in two out of five cases and DLA‐genotyping revealed novel haplotypes. Breed distribution differed between diabetic and non‐diabetic dogs. Reduced number of pancreatic islets and β‐cell mass were observed, with vacuolation of islet cells and ductal epithelium. In this population, where neutering is not standard practice, diabetes secondary to dioestrus is the most frequent diabetes subtype. Genetic susceptibility also differed from previous studies. These results support the heterogeneous pathogenesis of canine diabetes. [ABSTRACT FROM AUTHOR]

Abstract: We investigated molecular changes in the response to insulin in prostates of spontaneously developed (Bio Breeding) and streptozotocin (STZ)-induced diabetic rats that received sufficient amounts (euglycemic group), or suboptimal doses (hyperglycemic group) of insulin for 32 weeks, using Affymetrix GeneChip analysis of gene expression. Alterations in gene expression levels identified by microarray analysis, having potential biological relevance to prostate growth, were verified by real-time reverse transcription polymerase chain reaction (RT-PCR). A significant decrease in the weight of ventral prostate was observed in the hyperglycemic STZ-induced but not spontaneously developed diabetic group. Microarray analysis revealed that gene expression profiles were distinctly different in each region of the prostate, and that hyperglycemic diabetes in spontaneously developed and STZ-diabetic rats was associated with differential changes in the prostatic expression levels of 856 genes, of which 35 were related to cell growth, proliferation and death. RT-PCR data verified significant differences in the mRNA expression levels of Igfbp6, Tieg, and Clu between euglycemic and hyperglycemic groups, whereas expression levels of these genes in control and euglycemic diabetic groups were not significantly different. In ventral prostate, the mRNA expression levels of Igfbp6 and Tieg were significantly higher in the hyperglycemic STZ-induced diabetic than in the hyperglycemic spontaneously diabetic BBDP/Wor rats. Our data demonstrate that the diabetes induced by STZ in the BBDR/Wor rats affects prostate growth and the molecular response to insulin differently than that observed in BBDP/Wor rats that develop diabetes spontaneously. [Copyright &y& Elsevier]

To examine the differences between spontaneous and streptozotocin (STZ)-induced diabetes, four parallel studies were performed; three studies of diabetes-prone BB (BBDP/Wor) rats maintained for 8, 16, and 32 weeks and one study of STZ-injected diabetes-resistant BB (BBDR/Wor) rats maintained for 32 weeks. Each diabetic study has three groups of rats: a control group; a euglycemic group, which received sufficient amounts of insulin; and a hyperglycemic group, which received a suboptimal dose of insulin. The extent of tissue weight changes was generally shown to be less dramatic in the euglycemic diabetic than in the hyperglycemic diabetic rats. STZ-induced diabetes increased the bladder weight more dramatically (up to 3-fold) than did spontaneous diabetes (up to 2-fold). Furthermore, a significant decrease in the size of the adrenal gland (20%) and testis (10%) is observed only with spontaneous diabetes, whereas a significant decrease in the size of the ventral prostate (30%) is observed only with STZ-induced diabetes, although the serum testosterone levels are similar in both groups. Our data demonstrate that there are differences in the effect of insulin treatment on the tissue size of the genitourinary tract between spontaneously developed and streptozotocin-induced diabetes in BB rats. [ABSTRACT FROM AUTHOR]

To determine the involvement of calpains in human cataractogenesis, studies in aged animal models are needed. Aged, male WBN/Kob rats spontaneously develop cataract along with severe, persistent diabetes with hyperglycemia and nephropathy. The purpose of present experiments was to provide a biochemical mechanism for the involvement of ubiquitous calpains in cataractogenesis in WBN/Kob rats. Serum and urinary glucose were measured to confirm diabetes, and cataracts were observed by slit lamp biomicroscopy. Calcium determinations were performed on lens samples from several ages of WBN/Kob and Wistar rats. Casein zymography, immunoblot analysis for α-spectrin, calpain 2, and calpain 10 were performed to detect activation of calpain in lens samples. Serum glucose levels increased and cortical cataract developed in male WBN/Kob rats within 1 year, indicating diabetic cataract. Cataract was accompanied by several presumptive biochemical indicators of calpain activation, including increased calcium, proteolysis of α-spectrin, and decreased caseinolytic activity for calpains suggesting calpain activation followed by autolytic degradation. Activation of ubiquitous calpains may contribute to biochemical mechanism of cataractogenesis in spontaneously diabetic WBN/Kob rats. The WBN/Kob model may be useful for elucidating the roles of calpain 2 and calpain 10 in human cataractogenesis. [Copyright &y& Elsevier]

A study of the pancreatic islets of Langerhans in the Djungarian hamster ( Phodopus sungorus) was initiated by the observation that 98 percent of the animals of a recently established colony showed ketoacidosis soon after birth, about ten percent of which later developed persistent hyperglycemia. The islets are made up of a centrally located mass of insulin-producing B-cells surrounded by a peripheral rim of A-and D-cells. Most islets are richly supplied by unmyelinated nerve fibers which terminate on all three cell types with cholinergic synaptic endings. Early changes in islet fine structure due to ketosis comprise degranulation of A-cells combined with signs of crinophagia of α-granules. After the manifestation of hyperglycemia, degranulation of B-cells is followed by deposition of glycogen which in the late phase of the diabetic syndrome forms large masses obscuring the regular cellular organelles. In six-to nine-month hyperglycemic animals degenerative changes are also observed in D-cells in the form of autophagic vacuoles. [ABSTRACT FROM AUTHOR]

The present study describes the cytopathology of the pancreatic islets in 18-old male eSS rats with spontaneous diabetes mellitus as compared to aged-matched normal animals. Lightmicroscopic immunocytochemical and morphometric techniques were used to study islet-cell populations, while quantitative methods were employed specifically for the analysis of B-cell ultrastructure. The diabetic rats showed disruption of the islet structure and fibrosis in the stroma. The volume density (Vvi) of endocrine tissue and the Vvi and percentage of B cells were diminished, whereas the Vvi of exocrine tissue and the Vvi and percentage of D cells were increased. The number of medium and large islets as well as their mean volume (μm) decreased in these animals. Pancreatic B cells from eSS rats showed an increase in the Vvi of endoplasmic reticulum, immature secretory granules and lysosomes. Conversely, the Vvi of total secretory granules and microtubules appeared diminished. The current observations contribute to our understanding of this useful animal model of diabetes mellitus, in the attempt to clarify the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Rat liver microsomal Δ6 and Δ5 desaturation are defective in experimental diabetes, but this defect is correctable with insulin treatment. Rat liver fatty acid composition and Δ6 and Δ5 desaturation were studied in the spontaneously diabetic adult female Bio-Breeding (BB) rat. Control Wistar rats and BB rats (4 weeks of diabetes), that received insulin (1 IU·100 g body weight·day), were killed 20 h after the last insulin injection. Δ6 and Δ5 desaturase activities were estimated from the incubation of liver microsomes with (1-C) 18:2, n−6 or (2-C) 20:3, n−6, respectively, and the fatty acid composition of the liver and microsomal liver lipids were investigated. Under experimental conditions Δ6 and Δ5 desaturase activities were unchanged in the BB rats when compared to the control rats. Impairment of the liver fatty acid composition of diabetic BB rats is not consistent with normal desaturase activity and may be explained by factors other than desaturation disturbance. [ABSTRACT FROM AUTHOR]

Approximately 50% of BB rats develop insulinopenic hyperglycaemia and ketosis spontaneously in association with insulitis. Amelioration of the syndrome by immunosuppression suggests a cell mediated immune pathogenesis. Analysis of the cell-mediated immune profile of overtly diabetic and normoglycaemic diabetes prone BB rats indicates that they are lymphocytopenic relative to non-diabetes prone BB rats and that the T cell pool is particularly affected. Furthermore, lymphocytes from diabetic and diabetes prone BB rats, while producing normal responses to the T cell mitogen concanavalin A, do not respond when mixed in vitro with major histocompatibility complex incompatible lymphocytes. This anergy is not restored either by enriching the responding cell population for T cells or by adding exogenous T cell growth promoting factor. Thus BB rats have a numerical and regulatory deficit of their T cells which could be related to their propensity for diabetes. [ABSTRACT FROM AUTHOR]

Wound healing was examined in normal and diabetic, non-ketotic Chinese hamsters by morphological and morphometric methods. Dermal, perforating wounds were made in the ears of the hamsters and the response to injury was evaluated in tissue biopsies. The response in normal hamsters was characterized by vascular and cellular migration and pronounced infiltration of polymorphonuclear leukocytes into the area closest to the wound (zone 1). The transition region (zone 2) between wounded and non-wounded tissue was infiltrated primarily by fibroblasts and capillaries. In wounds from diabetic hamsters, 8 h after injury, there was less cellular infiltration (fibroblasts 49%, polymorphonuclear leukoytes 48% of control) and vascular proliferation (47% of control). In the late phase of healing (16 h after injury) the vascular (87% of control) and polymorphonuclear leukocyte (103%) responses in diabetic wounds were not significantly different from control in zones 1 and 2. Wounds from diabetic hamsters also showed considerable oedema (143% of control) in zones 1 and 2, which was accompanied by vascular degeneration and necrosis. At 16 h the collagen content of diabetic wounds was also decreased (54% of control). Increased oedema with reduced vascular proliferation and cellular infiltration in the early healing period characterises the response to injury in the diabetic Chinese hamster. [ABSTRACT FROM AUTHOR]

A longitudinal study of 51 weanlings from 5 litters of 'BB' Wistar rats was undertaken to characterize the time course of the spontaneous diabetic syndrome. Nine rats developed overt diabetes. An abnormal glucose tolerance preceded the onset of the syndrome in 6 of these 9 rats. No other 'clinical' or metabolic variable measured was predictive of the development of this syndrome. In these rats, the onset was remarkably abrupt, followed by rapid clinical deterioration with marked hyperglycaemia, glycosuria, ketonaemia and hypoinsulinaemia attained within 2 to 8 days. Pronounced insulitis was present in the early stages of the syndrome, resulting in complete B-cell destruction at the time of sacrifice at 7 to 40 days. Among the 42 littermates, 9 revealed sequential abnormalities in oral glucose tolerance tests performed at weekly intervals (to age 90-120 d) though remaining aglycosuric and maintaining normal fasting plasma glucose levels. In 7 of these rats, a milder form of the same islet inflammatory lesion seen in the overtly diabetic animals was present. Thus the new features identified are: 1) a time course of evolution from normoglycaemia to overt diabetes telescoped into a period of days, and 2) a 'chemical' stage or form with an insulitis similar to that found in the early stages of overt diabetes. [ABSTRACT FROM AUTHOR]

Primary hypersecretion of insulin has been suggested as one possibility for the genetic fault of ob/ob mice. To test this hypothesis, streptozotocin (SZO) was used to reduce permanently insulin secretion in young lean and obese mice. After establishment of hyperglycaemia and weight reduction in treated obese mice (obese-SZO), daily insulin replacement was begun in some (obese-SZO-Ins). Obese-SZO mice maintained insulin levels and body weights similar to lean controls, though they were shorter and fatter, while food intake and blood sugar levels exceeded lean values. Obese-SZO-Ins mice with reduced islet hyperplasia, but great insulin resistance, gained more weight than obese-SZO mice; had high serum insulin and controlled blood glucose; and exhibited hyperphagia. These results suggest that primary hypersecretion of insulin cannot be the genetic defect, as ob/ob mice are hyperphagic, hyperglycaemic, insulin resistant, and 'obese' even when insulin levels are restricted. [ABSTRACT FROM AUTHOR]

The pancreatic B-cell contains microtubules, which are thought to participate in the process of insulin release. In order to disclose a possible abnormality of this B-cell microtubular system in animals with islet dysfunction, isolated islets from normal rats and mice, as well as from diabetic mutant mice (DBM mice) and from spiny mice ( Acomys cahirinus) were incubated in the presence of vincristine, which causes the precipitation of the microtubular protein into paracrystalline deposits. Ultrastructural examination of the islets indicated that the volume-density of vincristine-induced deposits was markedly reduced in B-cells of spiny mice, when compared to that found in normal rats and mice and DBM mice. Exposure of the islets from spiny mice to a high glucose concentration, concomittantly to vincristine, caused a further reduction in vincristine-induced crystals content of the B-cell. It is speculated that an impairment of the B-cell microtubular system may account for the deficiency of insulin release found in spiny mice. [ABSTRACT FROM AUTHOR]

Increased activity of the polyol pathway for glucose metabolism and increased intracellular levels of glucose, polyol, and fructose have been implicated in the onset of chronic complications of diabetes in certain tissues where the transport of glucose is not insulin-dependent. Levels of all three carbohydrates were found to be significantly higher in sciatic nerves and lenses from diabetic and ketotic hamsters than in tissues from nondiabetic control animals ( p<0.01). Glucose, polyol, and fructose levels were not significantly different in spinal cords or gastrocnemius muscles from diabetic and ketotic hamsters than in tissues from nondiabetic hamsters. There was a linear relationship between blood glucose levels and tissue levels of glucose ( r=0.885), polyol ( r= 0.797), fructose ( r=0.886) and the total tissue concentration of all three substances ( r=0.916) in hamster sciatic nerves. Similarly, a linear correlation between blood glucose levels and levels of glucose ( r=0.934), polyol ( r=0.784), fructose ( r=0.866) and the total tissue concentration of the three carbohydrates ( r= 0.915) in lenses was also established. The results of these studies provide evidence that glucose, polyol, and fructose levels are elevated in certain tissues from animals with spontaneous diabetes. The significance of these observations with respect to the pathogenesis of complications of diabetes remains to be determined. [ABSTRACT FROM AUTHOR]

Light microscopic and autoradiographic studies were performed in normal genetic nondiabetic and diabetic Chinese hamsters after the administration of thymidine-H and correlated with levels of blood glucose (BG) and plasma insulin (IRI). Pancreatic islets of normal hamsters contained well granulated beta cells; rare islet cells incorporated thymidine-H and the IRI/BG ratio (I/G) was = 1.91. Recent onset diabetics revealed hyperglycemia and hyperinsulinemia (I/G = 1.97), beta cell degranulation and increased islet cell labelling. With progression of diabetes, I/G ratios decreased (Non-ketotic animals: 1.08, Ketotic hamsters: 0.17), beta cell numbers declined and islet labelling was infrequent. Hamsters with spontaneous remission from diabetes showed normoglycemia, hyperinsulinemia (I/G = 2.84) and beta cell hyperplasia. Glucocorticoid administration to normal hamsters induced marked BG elevations, beta cell hyperplasia and increased thymidine-H incorporation. The absence of increased beta cell labelling among most diabetics treated with glucocorticoids may be a manifestation of a genetically defined defect of beta cell replication that is in part responsible for the declining beta cell mass and insulin synthetic capacity of the diabetic Chinese hamsters. [ABSTRACT FROM AUTHOR]

Electron microscopic studies were performed on pancreatic islets of normal, genetic, nondiabetic Chinese hamsters and of diabetic animals of all degrees of severity. The ultrastructural appearance of the islets of normal hamsters did not differ from that of normal rats and mice. The islets of the profoundly diabetic animals could be distinguished because of the magnitude of beta cell glycogen infiltration, frequency of beta cell necrosis and decreased number of surviving beta cells. Islets of hamsters with spontaneous remission from diabetes contained increased numbers of hyperfunctioning beta cells. Surviving beta cells of all diabetic hamsters revealed ultrastructural evidence of enhanced insulin synthesis and secretion but revealed no evidence to suggest that they were insensitive to physiological stimuli or incapable of insulin synthesis. Spontaneous remission among diabetic Chinese hamsters could thus be explained, in part, on the basis of enhanced beta cell replication resulting in an increased insulin synthetic capacity. [ABSTRACT FROM AUTHOR]

The nuclear and plasma membranes of islet cells from non-glycosuric and diabetic Chinese hamsters were examined by freeze-etching. The B-cells of diabetic animals presented a slight increase in the number of nuclear pores and marked alterations in the number, size and distribution of membrane-associated particles in the plasma membrane. In A-cells, identified by the presence of characteristic bundles of coarse filaments in the perinuclear region, a definite increase in the number of nuclear pores was found in the most severely diabetic animals. These preliminary findings point to alterations in the membrane systems as possible determinants for the abnormalities of islet function in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Intracellular glycogen deposits were consistently found in the retina, kidney and pancreatic islets of diabetic-ketonuric Chinese hamsters. Accumulation of glycogen in the outer nuclear layer of the retina was mostly associated with severity of the disease, but was not related to age or sex. The type of retinal cell involved in the accumulation of glycogen was not clearly established. However, the position of the affected cell, side by side with retinal neurons, suggests that the glycogen deposits were within Müller cells. These giant glias normally synthesize and store glycogen. All ketonuric Chinese hamsters examined showed some accumulation of glycogen in distal tubules of the kidney. This abnormal glycogen was not found in glucosuric non-ketonuric or in nondiabetic Chinese hamsters. Variable amounts of glycogen were found in Β cells of pancreatic islets of diabetic hamsters, as reported by others. However, accumulation of glycogen was also found in α and D islet cells from 2 middle aged Chinese hamsters with long term glucosuria and recent ketonuria. Abnormal glucose and glycogen metabolism seem to play an important role in the pathogenesis of diabetes in the Chinese hamster. [ABSTRACT FROM AUTHOR]

Two aspects of protein synthesis were studied in vitro in tissue extracts prepared from normal, diabetic and ketotic Chinese hamsters. Firstly, the activity to support polyuridylic acid (poly U)-dependent polyphenylalanine synthesis fromC-phenylalaninet RNA was measured in the liver ribosomes and no significant difference was observed between diabetic hamsters (0.310±0.007 nCi/min/mg ribosomal proteins) and their controls (0.325±0.015), or between ketotic hamsters (0.256±0.013) and their controls (0.274±0.018). Secondly, activity in protein synthesis with endogenous mRNA's was followed in the postmitochondrial supernatant (PMS) fraction after the removal of endogenous amino acid pools by gel filtration. The rate of amino acid incorporation was measured in both liver and kidney extracts withC-leucine, lysine, serine, or glycine as labels. The initial rates of incorporations in the diabetic liver PMS ( Leu = 8.01±1.64 pmole/min/mg protein; Lys = 2.90±0.56; Ser = 3.40±0.60; Gly = 3.34±0.66), and in the ketotic PMS ( Leu = 8.48±2.06; Lys = 3.49±0.82; Ser = 4.11±0.80; Gly = 3.73 ±0.81) were similar to those in the matched controls ( Leu = 8.60±1.06; Lys = 3.14±0.37; Ser = 3.70±0.54; Gly = 3.38 ±0.37). Likewise, the amino acid incorporations in the diabetic kidney PMS ( Leu = 4.38 + 1.09; Lys = 1.26±0.28; Ser = 1.98±0.29; Gly = 1.81±0.32), and in the ketotic kidney PMS ( Leu = 5.39±1.29; Lys = 1.79±0.4; Ser = 1.9±0.18; Gly = 1.97±0.15) were not significantly different from those in the normals ( Leu = 5.32±0.56; Lys = 1.60±0.19; Ser = 2.06±0.22; Gly = 2.02±0.18). It is concluded that the diabetic and ketotic Chinese hamsters retain normal activity in the reported two aspects of protein synthesis. [ABSTRACT FROM AUTHOR]

Eighteen sand rats ( Psammomys obesus) maintained on a vegetable or mixed vegetable and laboratory chow diet were bled and their pancreases removed and incubated in vitro to study insulin release. Plasma glucose and insulin measurements showed that all the animals were either normal or had a mild non-ketotic diabetes mellitus-like syndrome. Pancreatic insulin content was high (13 to 20 U/g) and insulin release in basal medium was 5 to 25 times that occurring with pancreas pieces from common laboratory animals. Basal in vitro insulin release correlated with the plasma insulin value at the time of sacrifice. Glucose, tolbutamide and dibutyryl cyclic AMP did not significantly stimulate nor did dopamine inhibit insulin release from pancreases from normal or mildly diabetic sand rats. Glucagon, however, did significantly stimulate in vitro insulin release. Insulin secretion in the sand rat has unique control mechanisms. [ABSTRACT FROM AUTHOR]

Studies of immunoreactive insulin (IRI) secretion have been performed in vivo in NZO mice. After an overnight fast, plasma IRI levels were 2-5 times higher in NZO than in control white mice. The IRI response to arginine, 10 mg/kg IV or isoprenaline, 10 Μ/kg IV, was similar in time in the two mice, but IRI increments were greater in the NZO animals. With glucagon 1 Μg/kg IV or aminophylline 25 mg/kg IV the initial secretory response was delayed compared to control mice. Glucose 1.0 g/kg IV elicited a markedly attenuated initial response in NZO mice. When IRI responses were related to basal IRI levels, NZO mice showed smaller initial responses (1-5 min) to all agents tested. Later responses were comparable in the two groups when compared in this way. Diphenylhydantoin, 40 mg/kg administered intraperitoneally 30 min before glucose, 1.0 g/kg IV did not affect glucose-induced insulin secretion in control animals, but abolished it in the NZO mice. These observations suggest the existence of a defect in the IRI release mechanism of the NZO Β cell situated at a point in the stimulus secretion coupling mechanism common to all the agents examined. [ABSTRACT FROM AUTHOR]

Expanded studies on the spontaneous diabetes mellitus in Macaca, nigra provide additional support to analogies between this animal model and human diabetes. Abnormal signs include hyperglycemia, decreased clearance of glucose in intravenous tolerance tests, reduced insulin secretion and increased serum lipids (triglyceride, prebetalipoprotein and nonesterified fatty acids). Insulin secretory capacity is lost concomitant with amyloid infiltration into the islets of Langerhans; additional metabolic aberrations may also reduce insulin secretion or action. Secondary manifestations are atherosclerosis, thickened basement membranes of muscle capillaries, and cataracts. In all probability, a genetic predisposition in these monkeys is exacerbated by changes in diet and environment. [ABSTRACT FROM AUTHOR]

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)