Lipid lowering explains the insulin sensitivity enhancing effects of a thiazolidinedione, 5-(4-(2-(2-phenyl-4-oxazolyl)ethoxy)benzyl)-2,4 thiazolidinedione
| Autor: | W. T. Johnson, F. E. Yakubu-Madus, T. W. Stephens |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Endocrinology Diabetes and Metabolism Glucose uptake Type 2 diabetes Carbohydrate metabolism Glucagon chemistry.chemical_compound Endocrinology Insulin resistance Internal medicine Internal Medicine medicine Animals Insulin Obesity Thiazolidinedione Triglycerides Triglyceride business.industry Lipid metabolism medicine.disease Rats Rats Zucker Thiazoles Glucose chemistry Diabetes Mellitus Type 2 Liver Glucose Clamp Technique Female Thiazolidinediones Insulin Resistance business |
| Zdroj: | Diabetes, obesitymetabolism. 2(3) |
| ISSN: | 1462-8902 |
| Popis: | Summary Aim: Insulin resistance is a characteristic feature of type 2 diabetes and obesity. The present study examined the effects of TZD300512, a thiazolidinedione, on glucose and lipid metabolism in the fatty Zucker rat (fa/fa), a rat model of insulin resistance. Methods: TZD300512 was administered (2.0 mg/kg/day) in the diet for 1 week to chronically catheterized Zucker fa/fa rats. We measured triglyceride clearance rate and hepatic triglyceride output. We assessed baseline glucose metabolism, and insulin-mediated glucose uptake. We also determined whether the insulin sensitivity enhancing effects of TZD300512 could be reversed by infusion of Intralipid. Results: TZD300512 treatment markedly reduced fasting plasma triglyceride by 72% and non-esterified free fatty acids by 46%. Moreover, treatment significantly enhanced plasma triglyceride clearance (AUC; 60.36 ± 11.50 v 131.44 ± 18.45 m m/min), but hepatic triglyceride output was not altered. Drug treatment significantly reduced fasting plasma glucose by 25%, plasma insulin by 73%, and had no effect on glucagon levels. Glucose infusion rate (GIR) needed to maintain euglycemia during hyperinsulinemic clamp was significantly increased from 34.96 ± 3.94 μmol/kg/min to 123.80 ± 4.80 μmol/kg/min, while whole body glucose uptake was more than doubled (58.49 ± 2.86 control vs. 126.97 ± 3.8 treated μmol/kg/min). Insulin-induced suppression of hepatic glucose production was nearly complete with treatment. Intralipid infusion reversed drug-induced improvement in insulin sensitivity. Conclusions: These results suggest that TZD300512-favourable alterations in lipid metabolism have a significant impact on its effectiveness in enhancing insulin sensitivity in a severely insulin resistant rodent model of type 2 diabetes. |
| Databáze: | OpenAIRE |
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