Khalil Wjidan1, Effendi Ibrahim2, Brinnell Caszo3, Justin Gnanou3, Harbindarjeet Singh4. 1. Master's Student, Faculty of Medicine, Universiti Teknologi MARA , Sungai Buloh, Malaysia . 2. Lecturer, Faculty of Medicine, Universiti Teknologi MARA , Sungai Buloh, Malaysia . 3. Associate Professor, Faculty of Medicine and Defence Health, National Defence University of Malaysia , Kem Sungai Besi, Kuala Lumpur, Malaysia . 4. Professor, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia; I-PerFFORM, Universiti Teknologi MARA , Selayang Campus, Selayang, Kuala Lumpur, Malaysia .
Abstract
INTRODUCTION: Impaired glucose utilization is seen in chronic hyperleptinaemia associated conditions such as obesity and type 2 diabetes mellitus. It is unclear if this impaired glucose utilization is due to the effect of persistent hyperleptinaemia on insulin secretion from the beta cells of pancreas. AIM: To examine the effects of chronic leptin administration on plasma glucose regulation in rats. MATERIALS AND METHODS: Glucose challenge curves were plotted for male Sprague-Dawley rats treated with either normal saline (Control; n=8) or subcutaneous leptin injection for 42 days (60 μg/kg body weight/day; n=8). Plasma glucose and plasma insulin levels were measured at 0, 5, 10, 15, 20 and 25 minutes after glucose challenege. Skeletal muscle tissue was collected at the end of a glucose challenge for glucose transporter-4 protein content, insulin receptor and glucose transporter-4 mRNA expression. Data were analysed using repeated measures and one-way ANOVA with post-hoc analysis. RESULTS: Chronic leptin treatment caused significantly higher fasting insulin level. Post glucose challenge, there was a significant increase in blood glucose levels and insulin level in the leptin treated rats. There was no significant difference in the skeletal muscle glucose transporter-4 content. However, leptin treated rats showed decreased mRNA expression of Insulin Receptor and glucose transporter-4 in the skeletal muscle. CONCLUSION: Leptin administration for 42 days caused hyperinsulinaemia and decreased the expression of insulin receptors in insulin sensitive tissues leading to the development of an insulin resistance-like state in the rats.
INTRODUCTION: Impaired glucose utilization is seen in chronic hyperleptinaemia associated conditions such as obesity and type 2 diabetes mellitus. It is unclear if this impaired glucose utilization is due to the effect of persistent hyperleptinaemia on insulin secretion from the beta cells of pancreas. AIM: To examine the effects of chronic leptin administration on plasma glucose regulation in rats. MATERIALS AND METHODS:Glucose challenge curves were plotted for male Sprague-Dawley rats treated with either normal saline (Control; n=8) or subcutaneous leptin injection for 42 days (60 μg/kg body weight/day; n=8). Plasma glucose and plasma insulin levels were measured at 0, 5, 10, 15, 20 and 25 minutes after glucose challenege. Skeletal muscle tissue was collected at the end of a glucose challenge for glucose transporter-4 protein content, insulin receptor and glucose transporter-4 mRNA expression. Data were analysed using repeated measures and one-way ANOVA with post-hoc analysis. RESULTS: Chronic leptin treatment caused significantly higher fasting insulin level. Post glucose challenge, there was a significant increase in blood glucose levels and insulin level in the leptin treated rats. There was no significant difference in the skeletal muscle glucose transporter-4 content. However, leptin treated rats showed decreased mRNA expression of Insulin Receptor and glucose transporter-4 in the skeletal muscle. CONCLUSION:Leptin administration for 42 days caused hyperinsulinaemia and decreased the expression of insulin receptors in insulin sensitive tissues leading to the development of an insulin resistance-like state in the rats.
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