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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied whether obesity or inheritance was the more important factor in the development of non-insulin-dependent diabetes mellitus (NIDDM) using female Otsuka-Long-Evans-Tokushima Fatty rats (OLETF) possessing one of the diabetic genes, ODB-1, and male Long-Evans-Tokushima-Otsuka rats (LETO) possessing no ODB-1, neither of which were diabetic when bred normally. Diabetes-resistant male LETO rats and female OLETF rats (4 weeks old) were assigned to three groups of 6 rats each, respectively; two groups in which obesity was induced by high calorie 'cafeteria' diet (D), or ventromedial hypothalamus lesions (V) with normal chow diet and a control group fed on normal chow (C). Six male OLETF rats were used as NIDDM positive controls. The mean daily energy intakes of obese male LETO and female OLETF rats were higher than those of the respective C groups. At 27 weeks of age, the average body weights of the obese LETO and female OLETF rats were significantly higher than those of the respective C groups and similar to that of the male OLETF group. Abdominal fat deposits of the obese groups were significantly higher than those of the respective C groups. At 28 weeks of age, the cumulative incidence of diabetes mellitus in obese LETO rats was 0% in group D and 17% in group V, while that of obese female OLETF rats in groups D and V were 100%. At 29 weeks of age, the plasma immunoreactive insulin (IRI) responses to glucose in obese female OLETF rats, groups D and V, were higher than that in group C. In obese LETO rats, insulin-stimulated glucose disposal in vivo was similar to that in group C, but in obese female OLETF rats, it was reduced to 41% in group D and 37% in group V of that in group C. Sections of islets of the pancreas of obese LETO rats appeared histologically normal, whereas those of obese female OLETF rats showed enlarged multilobulated fibrotic islets. These results demonstrate that obesity is necessary, but not sufficient alone for the development of NIDDM in these rat models.
Diabetes Res Clin Pract 1995 Jul
PMID:Effects of obesity and inheritance on the development of non-insulin-dependent diabetes mellitus in Otsuka-Long-Evans-Tokushima fatty rats. 859 53

Exercise training has been shown to be effective in preventing the development of non-insulin-dependent diabetes mellitus (NIDDM) in a model rat (Otsuka-Long-Evans-Tokushima Fatty [OLETF]). For determination of how long a preventive effect of exercise training against the development of NIDDM lasts in this model, six male OLETF rats each were assigned to training (1) for a whole experimental period, from 7 to 28 weeks of age (E-E); (2) for the first half of the period, from 7 to 15 weeks of age (E-S); and (3) for the second half of the period, from 16 to 28 weeks of age (S-E). In addition, eight male OLETF rats were given no exercise during the experimental period (S-S). At 28 weeks of age, E-E, E-S, S-E, and S-S rats, weighed averages of 514, 542, 557, and 669 g and had abdominal fat deposits of 13.9, 21.3, 38.2, and 76.0 g, respectively. At 28 weeks of age, the cumulative incidence of NIDDM in S-S was 100%, while none of the trained rats were diabetic. The glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp test, an index of insulin sensitivity, in the E-E group was significantly greater than that in the S-S group. The values in the E-S and S-E groups were slightly, but not significantly, less than that in the E-E group. Morphologic studies on the pancreas of E-E rats and S-E rats showed minimal changes of islets, whereas sections of islets from E-S rats appeared slightly enlarged and fibrotic, although significantly less than those of islets of S-S rats. These results demonstrate that the preventive effect of excercise training against the development of NIDDM lasts for at least 3 months after the cessation of exercise in this model.
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PMID:Exercise training has a long-lasting effect on prevention of non-insulin-dependent diabetes mellitus in Otsuka-Long-Evans-Tokushima Fatty rats. 860 34

A long term study of diversity between two ethnic groups was developed in Evans County, Georgia. The findings are predicated on the genotypic-phenotypic interactions, with the multitude of environmental factors. The genetic-environmental interaction ultimately determines the individual's state of health or disease. For example, coronary heart disease prevalence and incidence rates were extremely low for blacks in Africa and four times lower than whites in rural South Georgia in the 1960s. Excessive hypertension and diabetes mellitus, and greater cerebrovascular disease mortality in black men, is now well known. Blood pressure levels studied in rural Africa were normal and did not rise with age, whereas blacks, conversely, demonstrated twice as much hypertension in South Georgia as whites and demonstrated an inverse relation between education and blood pressure (ie, the lower the education the higher the blood pressure). Cultural adaptation has accelerated hypertensive disease and strokes in blacks, while there remains an excess of atherosclerotic coronary heart disease in white men. Secular trends suggest that coronary heart disease is decreasing among white men but may be increasing in black men. Studies of ethnicity and biracial populations provide important cardiovascular disease associations with clinical risk factor studies.
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PMID:Ethnicity and cardiovascular disease: The Evans County heart study. 861 87

The mechanism behind the increased peritoneal permeability to albumin in diabetics is still unclear. In this study, streptozotocin diabetic rats developed albuminuria and significantly increased D/P of albumin after the fourth week of disease, reaching peak levels at the end of the 24 week period of follow-up. Coincidentally, extravasation of albumin to the interstitial tissue was evaluated with the Evans-blue method. Age-matched control rats showed Evans-blue concentrations of 0.023 +/- 0.013 micrograms/100 mg of dry tissue, whereas in diabetics the numbers were 1.22 +/- 0.719 micrograms (P < 0.001). Perfusion with Ruthenium-Red (RR) done in control at zero time, and in age-matched intact as well as in diabetic rats after 24 weeks of disease showed that the density distribution of capillary subendothelial anionic sites was significantly lower for diabetics (13 +/- 3/microns basement membrane vs. 31 +/- 3 and 34 +/- 4 in control groups; P < 0.001). Similar findings were made on the mesenteric submesothelial basement membrane. Mean density of RR decorated anionic sites was 12 +/- 2/microns basement membrane in diabetics, whereas those observed in both control groups were 31 +/- 2 and 31 +/- 3/microns (P < 0.001). Therefore, this reduced density of microvascular and submesothelial negative charges, equivalent to that induced by diabetes in other capillary beds, appears to be at the origin of the decreased permselectivity of the diabetic peritoneum for anionic serum albumin.
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PMID:Increased peritoneal permeability to albumin in streptozotocin diabetic rats. 864 11

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.
Diabetes 1996 Jul
PMID:Poor capacity for proliferation of pancreatic beta-cells in Otsuka-Long-Evans-Tokushima Fatty rat: a model of spontaneous NIDDM. 866 46

This work extends a recent observation that Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have been established as an animal model of non-insulin-dependent diabetes mellitus, show no expression of the cholecystokinin (CCK)-A receptor gene in the pancreas. The CCK-A receptor is known to be involved in regulating pancreatic exocrine function and growth. We examined the growth of the pancreas in terms of wet weight, enzyme compositions, and protein and DNA contents at 5-6 and 24-25 weeks of age in OLETF rats and control (Long-Evans Tokushima; LETO) rats. The pancreatic wet weight increased significantly with age in both OLETF and LETO rats but was significantly lower in OLETF rats than in LETO rats. The total DNA contents in the whole pancreas (cell numbers) were comparable for both strains and increased significantly with age. However, the ratio of protein content to DNA content (the cell size) significantly increased with age in LETO rats, with no increase in OLETF rats. The changes in chymotrypsin, amylase, and insulin with respect to age were in the same direction in both strains: a decrease or no change in total and/or cellular contents of chymotrypsin and insulin and increases in amylase. These results suggest that the CCK-A receptor plays some role in the increase in cell size associated with normal growth of the pancreas from 5 to 25 weeks of age (after weaning).
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PMID:Role of cholecystokinin (CCK)-A receptor for pancreatic growth after weaning: a study in a new rat model without gene expression of the CCK-A receptor. 874 Apr 1

Body fat distribution can be assessed by computed tomography (CT). The ratio of umbilicus was used to classify obese subjects as having visceral fat obesity (VFO) or subcutaneous fat obesity (SFO). Serum triglyceride and total cholesterol levels and plasma glucose area in an oral glucose tolerance test were higher in patients with VFO than in those with SFO. Significant positive correlations were demonstrated between V/S ratio and plasma glucose area, serum triglyceride level, and total cholesterol level as well as systolic or diastolic blood pressure. VFO was more frequently associated with coronary artery disease. Moreover, VFO was more often accompanied by multiple risk factors than was SFO. Steady-state plasma glucose (SSPG) level was significantly higher in patients with VFO than with SFO, suggesting that insulin resistance may be more remarkable in VFO than in SFO. Furthermore, visceral fat accumulation was also associated with these complications even in nonobese subjects. Visceral fat area (VFA) was significantly correlated with fasting plasma glucose, serum triglyceride, and total cholesterol levels. Animal models such as Goto-Kakizaki (GK) rats with ventromedial hypothalamus (VMH) lesions and Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were accompanied by visceral fat accumulation and an early stage of aortic atherosclerosis. Aging, sex hormone, genetic, and dietary factors and physical inactivity may induce visceral fat accumulation. Visceral fat is characterized by its high lipogenic activity as well as its accelerated lipolytic activity. High levels of portal free fatty acids (FFAs) may eventually result in an enhancement of hepatic triglyceride synthesis, causing hyperlipidemia. High portal FFA levels would also induce insulin resistance, thereby causing glucose intolerance, hypertension, and finally atherosclerosis. We propose a term, "visceral fat syndrome," as a highly atherogenic state, which includes visceral fat accumulation, glucose intolerance (insulin resistance), hyperlipidemia, and hypertension.
Diabetes Care 1996 Mar
PMID:Insulin resistance and body fat distribution. 887 8

It has been suggested that the unmyelinated small diameter afferent nociceptive C-fibres are impaired in diabetes mellitus. We have recently demonstrated that these fibres are the prerequisite for neurogenic inflammation induced by mechanical or chemical irritations. These experiments were designed to characterize the neurogenic inflammatory responses of gingivomucosal tissue in the early phase of experimental induced diabetes mellitus in rat. Effect of dental ligature on the gingivomucosal (GM) vascular permeability was studied in control rats and in rats pretreated with streptozotocin at d 7 and 14 following streptozotocin administration. In separate groups of control and streptozotocin diabetic rats studies were also performed to investigate the effect of local capsaicin application on GM vascular permeability on d 14. Vascular permeability was assessed by means of Evans blue extravasation. The ligature placed around the mandibular left first molar caused a significant increase vascular permeability of GM tissue on the ipsilateral side on both d 7 and 14 after the ligation in control rats. In streptozotocin diabetic rats on d 7, there was also a significant elevation of Evans blue extravasation in the tissue tested on the ligature side. However, on d 14 the ligation failed to produce any changes in Evans blue extravasation on the ipsilateral side, i.e. no difference in GM vascular permeability could be recorded between the two sides in streptozotocin diabetic rats. Topical capsaicin administration produced significant Evans blue extravasation in GM tissue of control rats compared to that observed in diabetic rats on d 14 after streptozotocin treatment. Electron microscopic and light microscopic studies demonstrated fibre degeneration of the C neurones and less inflammatory cells in streptozotocin-induced diabetes in the gingivomucosal tissue. These findings appear to indicate that the inflammatory responses induced by mechanical (dental ligature) and/or chemical irritants (topical application of capsaicin) in the gingivomucosal tissue are altered in streptozotocin diabetic rats and this alteration is due to the diabetes-induced damage to the unmyelinated C fibres.
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PMID:Effects of streptozotocin-induced diabetes on neurogenic inflammation of gingivomucosal tissue in rat. 881 94

To clarify whether ubiquitin is expressed in atherosclerotic lesions, and, if so, the expression is influenced by diabetes mellitus, we examined atherosclerotic (AS) lesions from Wistar fatty (WF) and Wistar lean (WL) rats immunohistochemically using an antibody against ubiquitin (AUb). Ten-week-old male WF and WL rats were treated to cannulize a silicon tube from the left carotid artery (LCA) to the descending aorta under chloral hydrate anesthesia and the tube was fixed. Age-matched WF and WL rats without cannulization were served as controls. Eight weeks after operation, 1 ml of 0.1% Evans blue solution was injected to all rats from the tail vein. 15 min latter, the aortae were removed, fixed with 4% paraformaldehyde and embedded in paraffin. Immunohistochemical staining with AUb by the ABC method, hematoxylin and eosin (HE) and elastica-Goldner (EG) stains were performed. In the cannulized group, focal areas of the luminal surface of the aorta were stained blue with Evans blue and these areas were microscopically confirmed as AS lesions in all WF and WL rats. In the control group, no Evans blue staining or AS lesions were observed. The destruction of the internal elastic lamina in AS lesions were seen with EG stain in the cannulized aorta of both WF and WL rats. No significant difference of the area ratio of intima/media was present between WF and WL rats in the cannulized group. Ubiquitin immunoreactivity was observed in the nucleus and cytoplasm of cells in AS lesions of both WF and WL rats. The present study suggests that ubiquitin plays a role in the formation of AS, and the condition of diabetes mellitus has little influence on ubiquitin expression and AS formation in this experimental model.
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PMID:Ubiquitin expression in atherosclerotic lesions of wistar fatty and wistar lean rats. 882 96

To determine whether improvement of insulin resistance decreases blood pressure as well as obesity, metformin (100 mg/kg/d) or vehicle was administered for 20 weeks to 12-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 10 each), a newly developed animal model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity, hyperinsulinemia, and hypertriglyceridemia. Oral administration of metformin ameliorated glucose intolerance and attenuated the insulin response to glucose loading (2 g/kg, i.p.), as evidenced by a decrease in the area under the curve for glucose and insulin at 24 weeks by 19% and 37%, respectively. At 21 weeks, systolic blood pressure was significantly lower in the metformin group than in controls (130 +/- 1.9 vs. 143 +/- 2.7 mmHg, p < 0.01), despite no difference in body weight. Subsequently, blood pressure tended to be slightly but insignificantly lower in the metformin group, and body weight was significantly lower in the metformin group (532 +/- 9.8 vs. 587 +/- 10.3 g at 31 weeks, p < 0.01). Metformin treatment also lowered the level of serum triglycerides (9.4 +/- 0.6 vs. 13.2 +/- 0.5 mmol/l, p < 0.01) and the plasma norepinephrine concentration (4,222 +/- 373 vs. 7,548 +/- 1,058 pg/ml, p < 0.01). These results suggest that metformin-induced improvement of insulin resistance in obese rats with NIDDM may lower blood pressure, as well as decrease sympathetic activity and reduce body weight.
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PMID:Metformin decreases blood pressure and obesity in OLETF rats via improvement of insulin resistance. 882 22


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