Femoral bone structure in Otsuka Long-Evans Tokushima Fatty rats

OBJECTIVES: Type 2 diabetes mellitus (T2DM) increases fracture risk despite normal to high levels of bone mineral density. Bone quality is known to affect bone fragility in T2DM. The aim of this study was to clarify the trabecular bone microstructure and cortical bone geometry of the femur in T2DM model rats. METHODS: Five-week-old Otsuka Long-Evans Tokushima Fatty (OLETF; n = 5) and Long-Evans Tokushima Otsuka (LETO; n = 5) rats were used. At the age of 18 months, femurs were scanned with micro-computed tomography, and trabecular bone microstructure and cortical bone geometry were analyzed. RESULTS: Trabecular bone microstructure and cortical bone geometry deteriorated in the femur in OLETF rats. Compared with in LETO rats, in OLETF rats, bone volume fraction, trabecular number and connectivity density decreased, and trabecular space significantly increased. Moreover, in OLETF rats, cortical bone volume and section area decreased, and medullary volume significantly increased. CONCLUSIONS: Long-term T2DM leaded to deterioration in trabecular and cortical bone structure. Therefore, OLETF rats may serve as a useful animal model for investigating the relationship between T2DM and bone quality.

Anti-diabetic effects of benfotiamine on an animal model of type 2 diabetes mellitus / 대한수의학회지

Although benfotiamine has various beneficial anti-diabetic effects, the detailed mechanisms underlying the impact of this compound on the insulin signaling pathway are still unclear. In the present study, we evaluated the effects of benfotiamine on the hepatic insulin signaling pathway in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are a type 2 diabetes mellitus model. OLETF rats treated with benfotiamine showed decreased body weight gain and reduced adipose tissue weight. In addition, blood glucose levels were lower in OLETF rats treated with benfotiamine. Following treatment with benfotiamine, the levels of Akt phosphorylation (S473/T308) in the OLETF groups increased significantly compared to the OLETF control group so that they were almost identical to the levels observed in the control group. Moreover, benfotiamine restored the phosphorylation levels of both glycogen synthase kinase (GSK)-3alpha/beta (S21, S9) and glycogen synthase (GS; S641) in OLETF rats to nearly the same levels observed in the control group. Overall, these results suggest that benfotiamine can potentially attenuate type 2 diabetes mellitus in OLETF rats by restoring insulin sensitivity through upregulation of Akt phosphorylation and activation of two downstream signaling molecules, GSK-3alpha/beta and GS, thereby reducing blood glucose levels through glycogen synthesis.

Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan / 당뇨병

BACKGROUND: Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. RESULTS: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 (TGF-beta1). CONCLUSION: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan.

Effects of exercise and dietary therapies on renal function and morphological findings in the kidney and glucose-fatty metabolism in oletf rats. Use of oletf rats as a model of type II diabetes mellitus / 体力科学

The effects of exercise and dietary therapy on the prevention of diabetic nephropathy (DN) were compared. Thirty-two male OLETF rats were divided into four groups (Ex, Diet, Sed, Pre) . Fourteen LETO rats served as the normal controls. Therapy was conducted for 10 weeks from age 22 to 31 weeks. The Ex group was trained by voluntary exercise, and the Diet group had a restricted food intake resulting in the same BW as that of the Ex group. The Ex developed a significant increase in urinary albumin excretion compared to the Diet group, although significantly less than the Sed group. Blood pressure in the Ex group showed a tendency to be higher during therapy. BW and serum lipids were significantly reduced, and glucose intolerance was improved in both the Ex and Diet groups. There were no differences in the metabolic indices between the Ex and Diet groups. The Ex group showed a significantly heavier kidney weight and a tendency for enlargement of the glomerular area and volume. The protective effect of DN through improvement of the metabolic dis-order by exercise might be offset by exercise-induced renal loads. Control of exercise intensity and blood pressure appear to be important as well as the improvement of glucose intolerance and lipid metabolisms in exercise therapy to prevent an occurrence and development of DN.

Influence of plasma lipid level on the accumulation of glomerular extracellular matrix in OLETF diabetic rats / 中国糖尿病杂志

Objective To investigate the effect of changes in plasma lipid levels on the accumulation of glomerular extracellular matrix in type 2 diabetic rats.Methods Rats were divided into three groups,namely,normal control,diabetes mellitus treated with Fenofibrate,which was gastrically administrated in the dose of 20mg?kg -1 ?d -1 for 22 weeks.A quantitative analysis of the components of glomerular extracellular matrix (ECM) were performed with immunoperoxide (ABC) method and the computer imagine analysis system.Results The result showed that diabetic rats had significantly higher plasma lipid levels and accumulation of ECM including collagen Ⅳ,laminine and fibronectin than the normal control ( P