Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new model of human non-insulin-dependent diabetes mellitus (NIDDM), we examined the role of local angiotensin II in cardiovascular and renal complications of NIDDM. OLETF rats were orally given cilazapril (an angiotensin-converting enzyme inhibitor, 1 or 10 mg/kg), E4177 (an angiotensin AT1 receptor antagonist, 10 mg/kg), or vehicle for 26 or 40 weeks (from the age of 20 to 46 or 60 weeks). Cardiac mRNAs were measured by Northern blot analysis, and the thickening of the coronary arterial wall and the degree of perivascular fibrosis were determined by an image analyzer. Cilazapril or E4177 did not significantly affect body weight or plasma glucose and insulin levels of OLETF rats, indicating the minor effects on diabetes itself. However, both drugs significantly and similarly prevented coronary microvascular remodeling (the increase in wall thickening and perivascular fibrosis in coronary arterioles and small coronary arteries) in OLETF rats, and they were associated with the suppression of cardiac transforming growth factor-beta1 expression. Both drugs suppressed not only the increase in left ventricular weight but also the downregulation of cardiac alpha-myosin heavy chain expression in OLETF rats. Glomerulosclerosis and glomerular hypertrophy in OLETF rats were improved by cilazapril and E4177 to a comparable extent. These results, taken together with the fact that OLETF rats show normal plasma renin levels, support that the AT1 receptor is involved in the pathogenesis of cardiac and renal complications in NIDDM.
 ...
PMID:Angiotensin blockade improves cardiac and renal complications of type II diabetic rats. 936 55

To investigate the role of increased polyol pathway activity and hemodynamic deficits in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human NIDDM, were given water with or without 30% sucrose and some of them were fed laboratory chow containing 0.03% cilostazol, an anticoagulant, or 0.05% [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (TAT), an aldose reductase inhibitor, for 8 wk. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. The peak latencies of oscillatory potentials of the electroretinogram in sucrose-fed OLETF rats were significantly prolonged compared with those in OLETF rats without sucrose feeding and LETO rats. There was a marked increase in platelet aggregability and a significant decrease in erythrocyte 2,3-diphosphoglycerate in sucrose-fed OLETF rats. Cilostazol significantly improved these parameters without changes in retinal levels of sorbitol and fructose. TAT, however, ameliorated all of these parameters. These findings confirm that the sucrose-fed OLETF rat is a useful animal model of retinopathy in human NIDDM and suggest that cilostazol improved diabetic retinopathy by modifying vascular factors, not by altering polyol pathway activity.
 ...
PMID:Electroretinogram in sucrose-fed diabetic rats treated with an aldose reductase inhibitor or an anticoagulant. 937 83

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese NIDDM. We performed a genome wide scan in F2 progenies obtained by crossing OLETF rats with two control strains, Long-Evans Tokushima Otsuka (LETO) and Fisher-344(F-344) rats. Since diabetes develops only in male progenies, we used only male F2 rats for the linkage studies.Highly significant linkage was observed between the phenotype, postprandial hyperglycemia and P-450ald locus on chromosome 1 and D7Mit 11 locus on chromosome 7. In addition, suggestive linkage was found between fasting glucose level and body weight and these two loci. Four other regions (D1Mit12, D2Mit11, D5Mgh14, and D17Arb1) on chromosome 1, 2, 5, and 17 were detected to influence body weight, fasting glucose level or postprandial hyperglycemia independently. We concluded that non-insulin-dependent diabetes mellitus(NIDDM) in OLETF rats is regulated by multiple genes which affect fasting, postprandial hyperglycemia, and obesity differently.
 ...
PMID:Genetic analysis of non-insulin-dependent diabetes mellitus in the Otsuka Long-Evans Tokushima Fatty rat. 940 57

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.
Diabetes 1998 Jan
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

To investigate cytoprotection against mucosal injuries of the stomach in patients with diabetes, we investigated gastric mucosal blood flow (GMBF), its response to a burn stress, and the involvement of nitric oxide (NO) in streptozotocin (STZ) diabetic rats. GMBF was measured by laser-Doppler velocimetry (LDV) and by the hydrogen gas clearance technique (HGC). The steady-state GMBF of STZ rats decreased according to the duration of diabetes, and insulin treatment blocked this decrease. Burn stress caused a rapid decrease in the GMBF. Reduction of the GMBF and gastric mucosal leakage of Evans blue (EB) after the burn stress were greater in the STZ rats than in the controls, but insulin treatment completely blocked this increase in EB leakage in the STZ rats. There was a significant negative correlation between the percent GMBF 3 h after the burn stress and EB leakage at the same time point. In the controls and the insulin-treated STZ rats, N-nitro-L-arginine (L-NNA), an NO synthase inhibitor, enhanced the decrease in postburn GMBF and EB leakage, but was without effect in the STZ rats. These results suggest that NO may be involved in the regulation of GMBF, and that persistent hyperglycemia may impair this regulation. These findings suggest that patients with diabetes have reduced cytoprotection against a variety of gastric mucosal injuries.
 ...
PMID:Gastric mucosal blood flow response to stress in streptozotocin diabetic rats: regulatory role of nitric oxide. 943 9

We measured abdominal fat masses (intra-abdominal visceral fat summing retroperitoneal, mesenteric, and epididymal fat and subcutaneous fat) and analyzed abdominal fat distribution of Otsuka Long-Evans Tokushima Fatty (OLETF) rats with non-insulin-dependent diabetes mellitus and control strain Long-Evans Tokushima Otsuka (LETO) rats using magnetic resonance imaging. Intra-abdominal visceral and subcutaneous fat were highly correlated with body weight both in OLETF and in LETO rats. Both intra-abdominal visceral and subcutaneous fat of OLETF rats significantly accumulated compared with those of LETO rats. Intra-abdominal visceral fat mass correlated positively with subcutaneous fat mass, and the accumulation of intra-abdominal visceral fat mass was about 3.5 times that of subcutaneous fat. Thus, obesity of OLETF rats was characterized by marked accumulation of intra-abdominal visceral fat compared with that of subcutaneous fat. Body weight and abdominal fat of OLETF rats were closely correlated with the level of total plasma glucose measured by oral glucose tolerance test. However the ratio of intra-abdominal visceral to subcutaneous fat of OLETF rats was not correlated with the level of total plasma glucose.
 ...
PMID:Measurement of abdominal fat by magnetic resonance imaging of OLETF rats, an animal model of NIDDM. 943 46

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to the effects of lard, olive oil, safflower oil, or distilled water as the control on the development of insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneous non-insulin-dependent diabetes mellitus (NIDDM) with obesity. After 17 or 18 weeks of treatment, the glucose infusion rate (GIR) in the euglycemic insulin-glucose clamp test only showed a significant increase in EPA-E-treated rats compared with control rats given distilled water alone as the vehicle. The GIR in EPA-E-treated animals was approximately three times greater than in the controls. This is the first report to display the influence of various fatty acids on the development of insulin resistance in OLETF rats. We demonstrated that EPA-E prevents the onset of insulin resistance, whereas olive oil and safflower oil have no effect and lard exacerbates insulin resistance. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase of the C18:2, C20:5, and C22:5 components in EPA-E-treated rats and, conversely, a significant decrease in C20:4. In addition, EPA-E-treated rats showed a significant increase in GLUT4 mRNA in skeletal muscle when compared with control rats. Our results indicate that the beneficial effect of EPA-E on insulin resistance in OLETF rats is likely to be dependent on modification of the phospholipid components of the skeletal muscle membrane. These findings suggest that dietary fatty acids may play a key role in the development of insulin resistance in patients with NIDDM.
 ...
PMID:Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus. 943 43

Bimoclomol (BRLP-42) is a novel antiischemic compound acting against peripheral vascular complications of diabetes mellitus (neuropathy, retinopathy, and nephropathy). In the present study the activity of bimoclomol was tested in experimental subarachnoid hemorrhage (SAH) and arachidonic acid (AA)-induced brain edema in rats to elucidate whether the compound may also have beneficial effect in cerebrovascular disturbances. For comparison, a neuroprotective AMPA antagonist, GYKI-52466, was examined. Injury caused by autologous intracranial blood injection or sodium-arachidonate was evaluated by the damage of blood-brain barrier (BBB) reflected in the extravasation of Evans blue dye into the cerebral tissue. Bimoclomol (2 x 2 mg/kg IV) markedly reduced, while GYKI-52466 (2 x 2 mg/kg IV) moderately diminished the extravasation produced by SAH (39.9%, p < 0.01 and 26.7%, p > 0.05, respectively). In the case of AA-induced brain edema, bimoclomol showed less pronounced (19.6%, p < 0.05) inhibitory action, and GYKI-52466 seemed to be more effective (34.2%, p < 0.05). These results suggest that bimoclomol may be active not only in peripheral micro- and macroangiopathy, but also in some types of cerebrovascular disorders.
 ...
PMID:Bimoclomol protects against vascular consequences of experimental subarachnoid hemorrhage in rats. 944 34

The liver plays a central role in lipoprotein metabolism. In particular, very-low density lipoprotein (VLDL) is assembled in the hepatocytes and secreted into the blood circulation. The VLDL is then catabolized to low-density lipoprotein by lipoprotein lipase and hepatic triglyceride lipase. Obese subjects, especially those with visceral fat accumulation, are frequently associated with hyperlipidemia, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. The mechanism of hyperlipidemia in visceral fat obesity has not yet been elucidated. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity with visceral fat accumulation, hyperlipidemia, and late-onset insulin resistance. To elucidate the mechanism of hyperlipidemia observed in OLETF rats, we focused on the production of VLDL by the liver and investigated hepatic messenger RNA (mRNA) levels of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A synthetase (ACS), and apolipoprotein B (apo B), which play important roles in VLDL synthesis and secretion. In 6-week-old OLETF rats, in which insulin resistance had not been manifested, visceral fat weight was already higher and portal free fatty acid (FFA) and VLDL-triglyceride levels were elevated compared with the control rats. Hepatic ACS activity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation before developing insulin resistance may be involved in the pathogenesis of hyperlipidemia in obese animal models with NIDDM.
 ...
PMID:Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation. 946 57

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are a new strain of spontaneous non-insulin-dependent diabetes mellitus (NIDDM) models. To evaluate the role of glucose transporters (GLUT) in the development of diabetes in this model, we examined the action of insulin on the translocation of GLUT4 and GLUT1 in isolated adipocytes, and the GLUT4 protein levels in muscles. Long-Evans Tokushima Otsuka (LETO) rats were used as a control strain. In adipocytes, the GLUT4 protein levels in OLETF rats at 30 weeks of age (diabetic stage) were considerably lower than those in LETO rats at the same age. At a pre-diabetic stage (7 weeks), there were no significant differences in GLUT4 protein levels in adipocytes between LETO and OLETF rats. However, the degree of GLUT4 translocation in OLETF rats was lower than that in LETO rats at 7 weeks of age. There were no differences in GLUT1 levels in adipocytes between the two strains. In muscles, the decrease in GLUT4 protein was observed in OLETF rats at 30 weeks of age. Whether such a difference is under the influence of hyperglycemia was also examined using rats rendered diabetic by 70% pancreatectomy. OLETF rats aged 7 weeks were subjected to partial pancreatectomy (Px) and sham pancreatectomy (sham). At 4 weeks after surgery, GLUT4 protein levels in adipose tissues and skeletal muscles were determined. GLUT4 decrease was observed for both tissues of hyperglycemic Px rats compared with euglycemic sham. Moreover, we examined the direct effect of glucose on GLUT4 protein using primary cultured adipocytes of OLETF rats at 5 weeks of age. After 7-day culture with normal (5.6 mmol/l) or high (25 mmol/l) concentrations of glucose, the GLUT4 protein levels in adipocytes decreased at 25 mmol/l glucose compared with 5.6 mmol/l glucose. These findings suggest an early defect in the insulin resistance of OLETF rats probably reflects impaired GLUT4 translocation. The GLUT4 decrease, which occurs later in the process appears to be a consequence, rather than a cause of diabetes in OLETF rats.
Diabetes Res Clin Pract 1997 Dec
PMID:Glucose transporter levels in a male spontaneous non-insulin-dependent diabetes mellitus rat of the Otsuka Long-Evans Tokushima Fatty strain. 948 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>