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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A spontaneously diabetic rat with polyuria, polydipsia, and mild obesity was discovered in 1984 in an outbred colony of Long-Evans rats, which had been purchased from Charles River Canada (St. Constant, Quebec, Canada) in 1982. A strain of rats developed from this rat by selective breeding has since been maintained at the Tokushima Research Institute (Otsuka Pharmaceutical, Tokushima, Japan) and named OLETF. The characteristic features of OLETF rats are 1) late onset of hyperglycemia (after 18 wk of age); 2) a chronic course of disease; 3) mild obesity; 4) inheritance by males; 5) hyperplastic foci of pancreatic islets; and 6) renal complication (nodular lesions). Histologically, the changes of pancreatic islets can be classified into three stages: 1) an early stage (6-20 wk of age) of cellular infiltration and degeneration; 2) a hyperplastic stage (20-40 wk of age); and 3) a final stage (at > 40 wk of age). These clinical and pathological features of disease in OLETF rats resemble those of human NIDDM.
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PMID:Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty (OLETF) strain. 139 18

The effect of probucol which acts as a scavenger of free radicals, on preventing the development of non-insulin dependent diabetes mellitus (NIDDM) in a model rat (Otsuka Long Evans Tokushima Fatty [OLETF]) was examined. Sixteen male OLETF rats aged 5 weeks were divided into two groups. One group were fed standard laboratory chow and the other group were fed the chow containing 1% probucol. At 12, 16, 24 weeks of age, an oral glucose tolerance test (OGTT) was performed. At 24 weeks of age, the cumulative incidences of diabetes mellitus in both groups were 100%. After two weeks, insulin-mediated glucose uptake was measured using a euglycemic clamp technique. There was no significant difference in glucose infusion rates between both groups. At the end of the experiment, plasma lipid concentrations were measured. The serum total cholesterol levels were significantly lower in rats fed probucol containing chow (66.3 +/- 3.7 mg/dl) than those of rats fed standard laboratory chow (78 +/- 6.4 mg/dl). On the other hand, the serum triglyceride level were not significantly different between them. Histological studies on the pancreas of both groups showed enlarged fibrotic islets and mononuclear cell infiltration in the periinsular area, though to a modest extent. These results demonstrated that probucol was not effective in preventing the development of NIDDM in this model animal. Considering these data, inflammatory destruction of pancreatic beta cells by free radical may not be involved in the development of NIDDM.
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PMID:The effect of probucol on the development of non-insulin dependent diabetes mellitus in Otsuka Long Evans Tokushima Fatty (OLETF) rats. 794 May 31

Morphological changes of the pancreas and impairment of pancreatic B-cell function in a model rat (Otsuka Long Evans Tokushima Fatty [OLETF]) with non-insulin dependent diabetes mellitus might be the result of over-activity of B-cells to compensate for insulin insensitivity. To test this possibility, we studied whether the histological and functional alterations in the pancreas of male OLETF rats were improved by treatment with insulin for a certain period, which might reduce the burden to B-cells. Groups of 6 male OLETF rats and 5 or 4 male non-diabetic control Long Evans Tokushima Otsuka (LETO) rats received injections of insulin (Ultralente MC; 10 U/kg/day to OLETF rats, 5 U/kg/day to LETO rats) or saline subcutaneously, once a day for 3 weeks from 24 weeks of age. Then their insulin responses to glucose (200 mg/dl) and arginine (10 mmol/l) were examined by perfusion of the pancreas. The morphological features of their pancreata were also examined. The insulin response to glucose in OLETF rats treated with insulin was significantly higher than that of OLETF rats treated with saline (sigma IRI 142.5 +/- 27.0 vs. 37.4 +/- 6.3 ng/ml.20 min, p < 0.05) and unlike in the latter showed the normal two phases. The morphological changes of the pancreas in the insulin-treated OLETF rats were remarkably ameliorated, animals showing no enlargement and only slight fibrosis of islets. Thus treatment with insulin was effective for preventing B-cell dysfunction and morphological changes of the pancreas in NIDDM model rats.
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PMID:Effect of timely insulin administration on pancreatic B-cells of Otsuka-Long-Evans-Tokushima-Fatty (OLETF) strain rats. An animal model of non-insulin dependent diabetes mellitus (NIDDM). 855 37

Expression of key regulatory enzymes involved in glucose metabolism was studied in the livers of Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin dependent diabetes mellitus. The activity and mRNA levels of glucokinase and L-type pyruvate kinase was increased in the liver of OLETF rats compared with control rats. There was no such remarkable change in liver-type phosphofructokinase. The activities of glucose-6-phosphatase and fructose-1,6-biphosphatase also increase despite high plasma levels of glucose and insulin. The activity of phosphoenolpyruvate carboxykinase did not show any significant change. The mRNA levels for fructose-1,6-biphosphatase, and phosphoenolpyruvate carboxykinase exhibited no marked changes. These results suggest that the expression of glucose-6-phosphatase and fructose-1,6-biphosphatase is disordered in OLETF rats.
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PMID:Disordered expression of hepatic glycolytic and gluconeogenic enzymes in Otsuka Long-Evans Tokushima fatty rats with spontanteous long-term hyperglycemia. 860 25

Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat, a genetic model of spontaneous development of NIDDM, exhibits hyperglycemic obesity with hyperinsulinemia and insulin resistance similar to that in humans. It is still unclear whether a defect in the beta-cell proliferation per se is the primary pathogenetic event in OLETF rat. To determine whether it is, we used partially pancreatectomized rats as a model, with administration of phlorizin to control blood glucose level, to examine whether the capacity for proliferation of beta-cells during hyperglycemia or normoglycemia differs between OLETF and their diabetes-resistant counterparts, Long-Evans-Tokushima-Otsuka (LETO) rats. We also examined whether such a defect, if present, could be improved by nicotinamide. Male rats, 6 weeks of age, were allocated at random to two groups: 70% pancreatectomy (Px) and sham-pancreatectomy (sham). Each group was divided into four subgroups by date of killing after surgery: 3-day, 7-day, 28-day (treated with phlorizin, nicotinamide, or saline), and 91-day. A sustained hyperglycemia was evident in the Px OLETF rats after surgery, which was associated with insufficient proliferation of beta-cells, characterized by decrease in beta-cell labeling index in proportion to decrease in beta-cell mass and reduction in insulin content in the remnant pancreas. This defect was unaffected by restoration of normoglycemia induced by phlorizin injection. Administration of nicotinamide, however, ameliorated the sustained hyperglycemia by increasing beta-cell proliferation. These findings suggest that OLETF rats have poor capacity for proliferation of pancreatic beta-cells and that this change may be the critical pathogenetic event before the onset of overt diabetes.
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PMID:Poor capacity for proliferation of pancreatic beta-cells in Otsuka-Long-Evans-Tokushima Fatty rat: a model of spontaneous NIDDM. 866 46

Levels of tissue advanced glycation end products (AGEs) that result from nonenzymatic reactions of glucose and proteins are high in both diabetic and aging people. Irreversible AGE formation is based on increases in AGE-derived protein-to-protein cross-linking and is considered to be a factor contributing to the complications of diabetes. A novel inhibitor of advanced glycation, OPB-9195, belongs to a group of thiazolidine derivatives, known as hypoglycemic drugs; however, they do not lower blood glucose levels. We did studies to determine if OPB-9195 would prevent the progression of nephropathy in spontaneous diabetic rats. In vitro inhibitory effects of OPB-9195 on AGE formation and AGE-derived cross-linking were examined by enzyme-linked immunosorbent assay (ELISA) and SDS-PAGE, respectively. Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of NIDDM, were used to evaluate the therapeutic effect of OPB-9195. Light microscopic findings by periodic acid-Schiff (PAS) staining, the extent of AGE accumulation detected by immunohistochemical staining in the kidneys, the levels of serum AGEs by AGE-specific ELISA, and urinary albumin excretion were examined. OPB-9195 effectively inhibited both AGE-derived cross-linking and the formation of AGEs, in a dose-dependent manner in vitro. In addition, the administration of OPB-9195 prevented the progression of glomerular sclerosis and AGE deposition in glomeruli. Elevation of circulating AGE levels and urinary albumin excretion were dramatically prevented in rats, even at 56 weeks of age and with persistent hyperglycemia. We concluded that a novel thiazolidine derivative, OPB-9195, prevented the progression of diabetic glomerular sclerosis in OLETF rats by lowering serum levels of AGEs and attenuating AGE deposition in the glomeruli.
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PMID:Progression of nephropathy in spontaneous diabetic rats is prevented by OPB-9195, a novel inhibitor of advanced glycation. 913 61

In an animal model of human non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed with sucrose for 8 weeks to obtain severe hyperglycemia. The effects of sucrose administration on peripheral nerve functions, motor nerve conduction velocity (MNCV) and coefficient of variance of R-R interval (CVR-R), were investigated with concomitant measuring of sciatic nerve blood flow (SNBF), ADP-induced platelet aggregation and polyol content in the sciatic nerves. The effects of an aldose reductase inhibitor, TAT, on these parameters were also studied. Administration of sucrose to OLETF rats caused significant body weight reduction and remarkable hyperglycemia. Sucrose-fed OLETF rats demonstrated significantly delayed MNCV, decreased CVR-R, reduced SNBF and increased platelet aggregation activity to ADP. Sorbitol and fructose accumulation, and myo-inositol depletion in sciatic nerves were observed only in sucrose-fed OLETF rats. These abnormalities were all ameliorated by the treatment with TAT. These observations suggest that the sucrose-fed OLETF rat is a useful animal model for studying the pathogenesis of diabetic neuropathy in human NIDDM, and that an aldose reductase inhibitor is a useful therapeutic agent for the treatment of diabetic neuropathy.
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PMID:Diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats: effect of an aldose reductase inhibitor, TAT. 915 94

To clarify the mechanism(s) of the antidiabetic effects of truncated glucagon-like peptide-1 (GLP-1) in diabetics, we examined its insulinotropic and extrapancreatic effects in a newly established strain of spontaneously non-insulin-dependent diabetic (NIDDM) rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, that received a continuous infusion of truncated GLP-1 620 pmol/d/kg (G group, n = 12) or of vehicle (V group, n = 12) for 4 weeks by Alzet pump. Nonfasting plasma glucose levels were significantly lower (P < .05) in the G group than in the V group (7.0 +/- 0.67 v 9.1 +/- 1.7 mmol/L), and fasting plasma immunoreactive insulin (IRI) levels were lower in the former than in the latter (0.63 +/- 0.31 v 0.78 +/- 0.25 nmol/L). At day 15 of infusion, the G group showed an attenuated plasma glucose response to an oral glucose load, but had plasma IRI levels comparable to those in the V group. A long-term infusion of truncated GLP-1 increased the glucose infusion rate (GIR) significantly (P < .05) during a euglycemic-hyperinsulinemic clamp test (59.0 +/- 14.8 mumol/kg/min for group G v 38.9 +/- 12.2 for group V), but hepatic glucose output (HGO) did not differ significantly for either group. Uptake of 2-deoxy-D-glucose (2DG) by peripheral muscles in the G group was as much as 2.4-fold higher than in the V group (5.52 +/- 2.04 v 2.29 +/- 0.97 mumol/100 g muscle weight/min). We conclude from these data that truncated GLP-1, in addition to its well-known incretin effect, is capable of augmenting insulin action in peripheral tissues of diabetics, which can contribute, in part, to improve glucose intolerance in OLETF rats.
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PMID:Extrapancreatic action of truncated glucagon-like peptide-I in Otsuka Long-Evans Tokushima Fatty rats, an animal model for non-insulin-dependent diabetes mellitus. 922 26

We investigated whether endothelial function may be impaired in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. The effect of exercise training and food restriction on endothelial function was also studied. OLETF rats were divided into three groups at age 16 weeks: sedentary, exercise trained, and food restricted (70% of the food intake of sedentary rats). Otsuka Long-Evans Tokushima rats were used as the age-matched nondiabetic controls. Endothelium-dependent relaxation of the thoracic aorta induced by histamine was significantly attenuated in the sedentary or food-restricted rats, and exercise training improved endothelial function. Relaxation induced by sodium nitroprusside, a donor of nitric oxide, did not differ significantly among groups. Both exercise training and food restriction significantly suppressed plasma levels of glucose and insulin and serum levels of triacylglycerol and cholesterol and reduced the accumulation of abdominal fat. Insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique, was significantly decreased in sedentary rats but was enhanced in exercise-trained and food-restricted rats. The urinary excretion of nitrite was significantly decreased in sedentary and food-restricted rats compared with nondiabetic rats and was significantly increased in exercise-trained rats. These results indicate that exercise training, but not food restriction, prevents endothelial dysfunction in NIDDM rats, presumably due to the exercise-induced increase in the production of nitric oxide.
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PMID:Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM. 942 78

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an obese non-insulin dependent diabetes mellitus (NIDDM) model of an inbred strain. In this study, basal (2.8 mM glucose) insulin and glucagon and their responses to glucose (16.7 mM) were examined at the age of 9 weeks (n = 3) before the onset of diabetes, at 23 weeks (n = 6) at the onset of diabetes, and at 48 weeks (n = 5) after the development of diabetes by pancreatic perfusion. In Long-Evans Tokushima Otsuka (LETO, control) rats, insulin responses to glucose showed a biphasic pattern at all three ages, while in OLETF rats, basal insulin concentrations were significantly increased compared to those in controls at the age of 9 and 48 weeks. Insulin responses to glucose showed no difference from controls at 9 and 23 weeks, however, at 48 weeks the response was significantly decreased. In controls, high basal glucagon concentrations showed significant decrease in response to glucose at all ages. In OLETF rats, basal glucagon concentrations showed significant decrease compared to those in control rats at 23 and 48 weeks. Glucagon response to glucose significantly decreased at 9 and 23 weeks, but at 48 weeks there was no change in concentration in response to glucose. Pancreatic insulin content was lower at 48 weeks in OLETF rats than in LETO rats, although no differences were observed at other ages. There were no significant differences in pancreatic glucagon content between the two groups at any age. Morphologically, in OLETF rats the number of pancreatic B cells were decreased and A cells migrated into the center of islets at 48 weeks. The results suggested that one of the causes of diabetes in OLETF rats is impaired insulin response to glucose.
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PMID:Alterations of insulin and glucagon secretion from the perfused pancreas before, at the onset and after the development of diabetes in male Otsuka Long-Evans Tokushima Fatty (OLETF) rats. 948 81


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