Dysregulation of glucose homeostasis following chronic exogenous administration of leptin in healthy sprague-dawley rats

• Main Authors: Caszo, B. (Author), Gnanou, J. (Author), Ibrahim, E. (Author), Singh, H. (Author), Wjidan, K. (Author)
• Format: Article
• Language: English
• Published: Journal of Clinical and Diagnostic Research 2015
• Subjects: animal experiment; animal model; Article; body weight; controlled study; enzyme linked immunosorbent assay; gene expression; glucose; glucose homeostasis; Glucose homeostasis; glucose tolerance; glucose transporter 4; GLUT 4; Hyperinsulinaemia; hyperinsulinemia; Hyperleptinaemia; hyperleptinemia; injection; insulin; insulin receptor; Insulin receptor; leptin; male; messenger RNA; muscle biopsy; nonhuman; rat; real time polymerase chain reaction; skeletal muscle
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 2249782X (ISSN)
• DOI: 10.7860/JCDR/2015/15594.7003

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. © 2015, Journal of Clinical and Diagnostic Research. All rights reserved.