UMLS:C0011860 - FACTA Search

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

To investigate the time course of the hepatic glucose metabolism in non-insulin-dependent diabetes (NIDDM), we measured hepatic glucose production (HGP) and first-pass uptake of portal glucose infusion by the liver (HGU) using dual-tracer methods in a NIDDM model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, and in normal controls, Long-Evans Tokushima Otsuka (LETO) rats, at 8, 14, and 28 weeks of age (n = 5, respectively). The fasting plasma glucose level in OLETF rats was significantly higher than in LETO rats at 28 weeks of age (8.9 +/- 1.7 v 6.3 +/- 0.4 mmol/L, P < .01), while there was no significant difference at 8 and 14 weeks. Hyperinsulinemia in OLETF rats appeared at > or = 8 weeks of age. Basal HGP was significantly higher in OLETF than in LETO rats at 8 and 28 weeks (8 weeks, 12.7 +/- 1.7 v 9.4 +/- 1.8 mg x kg(-1) x min(-1), P < .05; 28 weeks, 10.9 +/- 1.6 v 7.1 +/- 1.3 mg x kg(-1) x min(-1), P < .01). At 14 weeks, basal HGP was not significantly different between OLETF and LETO rats. However, at all study points, HGU during a portal glucose infusion was significantly lower in OLETF than in LETO rats (8 weeks, 0.9 +/- 0.2 v 2.3 +/- 0.5, P < .01; 14 weeks, 0.8 +/- 0.3 v 1.4 +/- 0.3, P < .05; 28 weeks, 0.7 +/- 0.2 v 1.4 +/- 0.3 mg x kg(-1) x min(-1), P < .01). Fasting plasma free fatty acid (FFA) levels were not significantly different between OLETF and LETO, except at 8 weeks. Suppression of plasma FFA levels by endogenous insulin during a portal glucose infusion was impaired in OLETF rats compared with LETO rats. In summary, this study demonstrates that derangement of hepatic glucose handling, such as increased basal HGP and decreased HGU, is observed in obese NIDDM model OLETF rats at the prediabetic phase when hyperglycemia is still not apparent. Furthermore, these derangements may be accompanied by impaired lipid metabolism.
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PMID:Increased hepatic glucose production and decreased hepatic glucose uptake at the prediabetic phase in the Otsuka Long-Evans Tokushima fatty rat model. 971 84

Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of NIDDM, is normoglycemic at a young age. However, they become hyperglycemic, even at a young age as a result of a 70% pancreatectomy, which is associated with insufficient proliferation of beta-cells. Administration of nicotinamide ameliorates the sustained hyperglycemia by increasing beta-cell proliferation. In order to further understand its mode of action, we studied how long nicotinamide is effective, in terms of ameliorating hyperglycemia, as evidenced by an increase in beta-cell mass, after its administration, in partially pancreatectomized OLETF rats. Male rats, 6 weeks of age, were allocated at random to two groups, 70% pancreatectomy (Px) and sham-pancreatectomy (sham). The Px group was divided into three subgroups, based on treatment with either nicotinamide (350 mg/kg), phlorizin (400 mg/kg) or saline, which continued until 4 weeks after surgery, and were sacrificed at 4, 6, or 8 weeks after surgery. A 70% Px resulted in sustained hyperglycemia in the saline-treated Px rats, which was ameliorated by administration of either phlorizin or nicotinamide, showing the non-fasting blood glucose levels reached to or near the levels found in the sham rats. After cessation of phlorizin injection, non-fasting blood glucose level increased rapidly, reaching the level of the saline-treated Px rats at the end of the experiment, whereas after cessation of nicotinamide injection, non-fasting blood glucose increased gradually to a level which was significantly lower than that observed in the saline-treated Px rats. An increased beta-cell mass, 62.7 +/- 7.8% of total beta-cell mass induced by nicotinamide at 4 weeks, decreased gradually, reaching the level of pretreatment, 30.3 +/- 4.0% 4 weeks after cessation of the treatment. The findings in this study suggest that ameliorated hyperglycemia as a result of proliferated beta-cells during the administration of nicotinamide may results in showing beta-cell exhaustion (a majority of beta-cell degranulation) once stopping injection, as compared with phlorizin treated group in this model rat.
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PMID:A role of nicotinamide-induced increase in pancreatic beta-cell mass on blood glucose control after discontinuation of the treatment in partially pancreatectomized OLETF rats. 976 66

Leptin, the product of the ob gene, has been reported to regulate feeding behavior and energy metabolism. Plasma leptin concentration was strongly correlated with body fat content in humans. It is well known that increased body fat content is accompanied by insulin insensitivity. In order to study the relationship between serum leptin level and metabolic variables, we performed caloric restriction on Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of noninsulin dependent diabetes mellitus. The male OLETF rats were allocated at random to three groups: 100% group, and 85% and 70% groups (which consumed 85% and 70% of the amount of food consumed by the 100% group, respectively). A significant correlation between serum leptin level and the body fat content, body weight, triglyceride, and fasting plasma glucose was observed. Using a partial correlation analysis to control for body fat content, however, the correlation between serum leptin and these variables disappeared. No significant changes in serum leptin levels were observed before and after a 1 h hyperinsulinemic euglycemic clamp test. In conclusion, serum leptin was significantly correlated with body fat content rather than fasting plasma glucose, serum insulin and insulin sensitivity. This suggests that circulating leptin per se may not result in hyperinsulinemia and insulin insensitivity in the OLETF rat.
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PMID:Circulating leptin did not associate with the development of the hyperglycemia accompanied by insulin insensitivity in spontaneous noninsulin dependent diabetes mellitus model Otsuka-Long-Evans-Tokushima-Fatty rats. 980 8

Non-insulin-dependent diabetes mellitus (NIDDM) is a prototypical multifactorial disease. Genetic predisposition and obesity are major risk factors for NIDDM development and the interactions between these factors are likely to be important in the etiology of this disease. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is one of the best animal models of NIDDM, since the OLETF rat develops NIDDM with mild obesity that is very similar to human NIDDM. Therefore, the OLETF rat is a powerful model for investigating the interaction between genetic susceptibility to NIDDM and obesity. In this study, our goal was to clarify the relationship between an individual NIDDM susceptibility locus and obesity in the OLETF using a molecular genetics approach. We identified four novel quantitative trait loci (QTLs) that contribute to the susceptibility to NIDDM, none of which shows significant linkage with body weight. However, Nidd1/of on chromosome 7 and Nidd2/of on chromosome 14 have an interaction with body weight. In contrast, one locus was mapped to chromosome 10 for body weight, but not to fasting or postprandial glucose levels. These data illustrate that NIDDM and body weight are under separate genetic control in the OLETF yet interact to yield the final disease phenotype in the two Nidd/of loci. In addition, body weight could be used in place of body mass index as an indicator of obesity in our experimental system of genetic study. This study will facilitate the understanding of the complex interaction between genetic susceptibility to NIDDM and obesity.
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PMID:Identification of quantitative trait loci for non-insulin-dependent diabetes mellitus that interact with body weight in the Otsuka Long-Evans Tokushima Fatty rat. 982 37

To clarify the relationship between diabetes mellitus and carbohydrate digestion, the activities of sucrase and isomaltase, which form a complex enzyme (SI complex) on the brush border membranes, were compared in the progression of diabetes mellitus in Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus with insulin resistance, and Long-Evans Tokushima Otsuka (LETO) rats as non-diabetic controls. Until 40 weeks of age, OLETF rats were obese and had a high plasma glucose level, compared to age-matched LETO rats, but the sucrase and isomaltase activities showed no significant differences between the two strains. Oral glucose tolerance test revealed that during 40-48 weeks of age, NIDDM became very severe with advancing insulin resistance in OLETF rats. In OLETF rats, in contrast to LETO rats, at 48 weeks of age, abnormal increases in the sucrase and isomaltase activities occurred, along with a remarkable decrease in body weight and a further great increase in the plasma glucose level in the non-fasting state. Hyperinsulinemia occurred in 20-week-old OLETF rats; however, at 40 and 48 weeks of age, the plasma insulin level in the non-fasting state in OLETF rats was not significantly different from that in LETO rats. The level of mRNA encoding the SI complex increased abnormally in 48-week-old OLETF rats. These results suggest that the advance of insulin resistance leads to an increase in the expression of the SI complex on the transcriptional level.
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PMID:Disordered expression of the sucrase-isomaltase complex in the small intestine in Otsuka Long-Evans tokushima fatty rats, a model of non-insulin-dependent diabetes mellitus with insulin resistance. 987 8

1. The influence of angiotensin-converting enzyme (ACE) inhibitor is investigated in enalapril on renal function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneously non-insulin-dependent diabetes (NIDDM). 2. Enalapril (5 mg/kg) or vehicle was administered once daily by gastric gavage to 22-week-old male OLETF rats for 32 weeks. Blood pressure, albuminuria, creatinine clearance, plasma glucose, serum insulin and lipids were determined before and during the treatment. Renal haemodynamics was examined at the end of the treatment. 3. Enalapril lowered blood pressure mildly but significantly. In the vehicle-treated rats, urinary albumin excretion increased from 0.75 +/- 0.16 mg/mg creatinine (Cr) to 8.65 +/- 0.78 mg/mg Cr. Enalapril significantly blunted the development of albuminuria from 0.66 +/- 0.12 mg/mg Cr to 5.19 +/- 0.67 mg/mg Cr (P < 0.008) without significant influence on creatinine clearances. Enalapril also significantly blunted the rise in serum cholesterol and triglyceride prior to the development of massive albuminuria. Enalapril did not affect bodyweight, plasma glucose or insulin levels. Renal haemodynamics assessed by inulin and p-aminohippuric acid clearances were similar in both groups at the end of the treatment. 4. These results reconfirmed that the ACE inhibitor has protective effects on nephropathy in NIDDM. Massive albuminuria was preceded by increase in serum lipids in OLETF rats, which supports the view that hyperlipidaemia exacerbates glomerular injury in chronic renal disease. Enalapril attenuated the rise in serum lipids, suggesting that the beneficial effects of the compound on renal injury in OLETF rats might also be mediated through the action of affecting serum lipids.
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PMID:Hyperlipidaemia and the progression of nephropathy in OLETF rats: effect of angiotensin-converting enzyme inhibitor, enalapril. 1047 73

Thromboxane (TX) A2 plays important roles on renal injuries in streptozotocin (STZ)-induced diabetic rats, whereas its role on the renal injuries in non-insulin-dependent diabetic (NIDDM) rats remains unknown. We evaluated the effects of an intravenous infusion of TXA2 synthetase inhibitor (OKY-046, 6 mg/kg/h) on the clearances on inulin and para-aminohippurate (Cin, C(PAH)) in a spontaneously NIDDM rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 8), and Long-Evans Tokushima Otsuka (LETO) rats (n = 7), served as control rats, at the age of 40-44 weeks. OLETF rats showed obesity, moderate hyperglycemia, and hyperinsulinemia. Urinary excretion of TXB2 was slightly higher and the ratio of TXB2 to 6-keto prostaglandin F1alpha (6-kPG) was significantly higher in OLETF rats (TXB2/6-kPG: 0.22 +/- 0.04 versus 0.12 +/- 0.02, P < 0.05). Both Cin and C(PAH) were significantly higher in OLETF rats than in LETO rats (Cin: 1.1 +/- 0.1 versus 0.7 +/- 0.1 mL/min/100 g BW, C(PAH): 3.1 +/- 0.2 versus 2.3 +/- 0.3 mL/min/100gBW, P < 0.01). OKY-046 did not restore Cin and C(PAH) in OLETF rats although it significantly decreased urinary excretion of TXB2, and thus ameliorated TXB2/6-kPG in OLETF rats. These data suggested that TXA2 was not involved in the renal hyperfiltration in OLETF rats at the age of 40-44 weeks, and that TXA2 might contribute to renal injuries in OLETF rats through mechanisms other than hemodynamic injury.
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PMID:Effect of acute thromboxane A2 inhibition on the renal hemodynamics in a spontaneously non-insulin-dependent diabetic rat, Otsuka Long-Evans Tokushima Fatty rat. 1061 56

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new diabetic strain of rats whose disease closely resembles human type 2 diabetes. We measured plasma adrenocorticotropic hormone (ACTH) and corticostrone levels, and iodine-125-labeled ovine corticotropin-releasing factor ([125I]oCRF) binding in the anterior pituitary after ether-laparotomy stress in OLETF rats to examine the alteration of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, we examined ACTH secretion following CRF administration in vivo and in vitro to characterize the mechanisms regulating the HPA axis in OLETF rats. Body weight, plasma glucose and insulin levels in OLETF rats were significantly higher than that in Long-Evans Tokushima Otsuka (LETO) rats. Basal plasma ACTH levels tended to be higher in OLETF rats than in LETO but it did not reach statistical significance. Ether-laparotomy stress dramatically increased plasma ACTH levels at 2 h after the stress both in either OLETF and LETO rats; the peak plasma ACTH level in OLETF rats following the stress was significantly greater than in LETO rats. Plasma ACTH levels following CRF (2 microg/kg, i.v.) in OLETF and LETO rats showed statistically significant increases at 10 and 30 min after CRF administration compared to ACTH levels at 0 min, however, the peak plasma ACTH level in OLETF rats at 10 min after CRF administration was significantly greater than in LETO rats. In contrast to ACTH levels, no significant differences in corticosterone levels between OLETF and LETO were observed at any of the time points. CRF (10 ng/ml) significantly increased ACTH secretion in pituitary cultures from OLETF compared to LETO rats. These data reveal a complex regulation of the endocrine system in this diabetic condition and suggest that HPA axis may be more stimulated during acute stress in diabetes mellitus than in unaffected subjects.
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PMID:Increased adrenocorticotropin responses to acute stress in Otsuka Long-Evans Tokushima Fatty (type 2 diabetic) rats. 1066 2

In an investigation of the involvement of prostanoids in the pathogenesis of nephropathy in type 2 diabetes, we repeatedly measured the urinary excretion of prostanoids in both diabetic and healthy rats as the rats aged. Seven rats of the Otsuka Long-Evans Tokushima Fatty strain were used as rats with a model of type 2 diabetes and seven rats of the Long-Evans Tokushima Otsuka strain were used as rats without diabetes. Thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1alpha, the amounts of which reflect renal production of TXA2 and PGI2, respectively, and PGE2 in urine collected in metabolic cages were assayed when rats were 14, 30, 46, and 54 weeks old. Plasma glucose and urinary protein excretion also were measured periodically. The mean plasma glucose concentration of the diabetic rats was higher than that of the healthy rats throughout the study. At 30 weeks and later, urinary protein excretion by the diabetic rats was greater than that of the healthy rats, and it increased with age. Urinary excretion of TXB2 by the diabetic rats was higher than that of the healthy rats at 14 weeks (52.4+/-23.5 vs. 27.0+/-2.6 ng/day; mean +/- SD, P = .015) and the difference continued to the end of the experiment. Urinary excretion of 6-keto-PGF1alpha by the diabetic rats was high at 14 weeks (52.3+/-12.8 vs. 26.9+/-4.6 ng/day; mean +/- SD, P<.001) but decreased with age and was the same as that of the healthy rats at 54 weeks. The urinary excretion of PGE2 by the two groups of rats was not significantly different. These results suggest that altered renal production of TXA2 and PGI2 is involved in the pathogenesis of diabetic nephropathy in rats with type 2 diabetes.
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PMID:Renal production of thromboxane and prostaglandins in a rat model of type 2 diabetes. 1067 Aug 25

Among the antihypertensive drugs, fast-acting Ca2+ antagonists have been reported to worsen insulin sensitivity. This effect may be attributable to reflex increases in sympathetic activity. On the other hand, however, it has been reported that long-acting, dihydropiridine Ca2+ antagonists improve insulin-resistance. The purpose of this study was to investigate whether cilnidipine, another long-acting dihydropidine Ca2+ antagonist, improves insulin sensitivity in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. 25 weeks OLETF rats were divided into the following groups; normal-diet group, cilnidipine-supplemented group (cilnidipine 3 mg/kg/day) and angiotensin II receptor antagonist CS-866-supplemented group (CS-866 1 mg/kg/day). As a non-diabetic control, we used Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Glucose infusion rate (GIR), an index of insulin resistance, as measured by the hyperinsulinemic euglycemic clamp technique was significantly decreased in OLETF rats. Cilnidipine-treatment partially but significantly improved insulin sensitivity in addition to systolic blood pressure in OLETF rats at 30 weeks of age, although it did not decrease accumulation of abdominal fat or serum levels of glucose or insulin. CS-866, an angiotensin II receptor antagonist, which lowers blood pressure through a different mechanism, did not improve insulin resistant states in OLETF rats. These results suggest that cilnidipine has a beneficial effect on insulin-resistance together with the antihypertensive effect.
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PMID:Cilnidipine improves insulin sensitivity in the Otsuka Long-Evans Tokushima fatty rat, a model of spontaneous NIDDM. 1068 61

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