Publications (2)13.63 Total impact
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Article: Apolipoprotein E deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus.
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ABSTRACT: Although it is known that lipid metabolism plays a role in insulin resistance in type 2 diabetes and in obesity, the mechanism is still largely unknown. Apolipoprotein E (ApoE) regulates plasma lipid levels and also plays a role in the uptake of lipids into various tissues. To investigate whether the suppression of whole-particle lipoprotein uptake into tissues affects insulin responsiveness and the diabetic condition, we examined the effect of an ApoE (also known as Apoe) gene deletion in MKR mice, a mouse model of type 2 diabetes. ApoE ( -/- ), MKR, ApoE ( -/- )/MKR and control mice were placed on a high-fat, high-cholesterol diet for 16 weeks. Glucose tolerance, serum insulin, blood glucose, insulin tolerance, tissue triacylglycerol content and atherosclerotic lesions were assessed. ApoE ( -/- )/MKR and ApoE ( -/- ) mice showed significantly improved blood glucose, glucose tolerance and insulin sensitivity. Reduced triacylglycerol content in liver and reduced fat accumulation in liver and adipose tissue were found in ApoE ( -/- )/MKR and ApoE ( -/- ) mice compared with control and MKR mice. ApoE ( -/- ) and ApoE ( -/- )/MKR mice demonstrated similarly large atherosclerotic lesions, whereas MKR and control mice had small atherosclerotic lesions. We demonstrated that ApoE deficiency abrogates insulin resistance in a mouse model of type 2 diabetes, suggesting that lipid accumulation in tissue is a major cause of insulin resistance in this mouse model.Diabetologia 06/2009; 52(7):1434-41. · 6.81 Impact Factor -
Article: Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes.
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ABSTRACT: The aim of this study was to examine the effects of thiazolidinediones on the MKR mouse model of type 2 diabetes. Six-week-old wild-type (WT) and MKR mice were fed with or without rosiglitazone or pioglitazone for 3 weeks. Blood was collected from the tail vein for serum biochemistry analysis. Hyperinsulinaemic-euglycaemic clamp analysis was performed to study effects of thiazolidinediones on insulin sensitivity of tissues in MKR mice. Northern blot analysis was performed to measure levels of target genes of PPAR gamma agonists in white adipose tissue and hepatic gluconeogenic genes. Thiazolidinedione treatment of MKR mice significantly lowered serum lipid levels and increased serum adiponectin levels but did not affect levels of blood glucose and serum insulin. Hyperinsulinaemic-euglycaemic clamp showed that whole-body insulin sensitivity and glucose homeostasis failed to improve in MKR mice after rosiglitazone treatment. Insulin suppression of hepatic endogenous glucose production failed to improve in MKR mice following rosiglitazone treatment. This lack of change in hepatic insulin insensitivity was associated with no change in the ratio of HMW : total adiponectin, hepatic triglyceride content, and sustained hepatic expression of PPAR gamma and stearoyl-CoA desaturase 1 mRNA. Interestingly, rosiglitazone markedly enhanced glucose uptake by white adipose tissue with a parallel increase in CD36, aP2 and GLUT4 gene expression. These data suggest that potentiation of insulin action on tissues other than adipose tissue is required to mediate the antidiabetic effects of thiazolidinediones in our MKR diabetic mice.Diabetologia 01/2005; 47(12):2215-25. · 6.81 Impact Factor
