Establishment of long-term high-fat diet and low dose streptozotocin-induced experimental type-۲ diabetes mellitus model of insulin resistance and evaluation of seed extracts of Syzygium cumini

Introduction: The principal mechanism responsible for reducing blood glucose is through insulin-stimulated glucose transport into skeletal muscle. The transporter protein that mediates this uptake is GLUT-۴. A defect in this step is associated with reduced glucose utilization in muscle and adipose tissue, as observed in insulin-resistant type-۲ diabetes mellitus (T۲DM) patients. This study aimed to develop an experimental T۲DM model and evaluate altered glucose transporter type ۴ (GLUT-۴) levels as a biomarker of insulin resistance. Antidiabetic activities of Syzygium cumini hydro-ethanolic seed extracts (SCE) were also evaluated. Methods: Adult male Wistar albino rats were fed a high-fat diet for ۱۲ weeks and dosed intraperitoneally with streptozotocin (۳۵ mg/kg). After treatment for ۲۱ days, all investigations were done. The homeostasis model of assessment (HOMA) was used for the calculation of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) index. Diaphragm muscle and retroperitoneal fat were collected for real-time polymerase chain reaction (RT-PCR) studies. Results: A significant increase in fasting blood glucose, HOMA-IR, and serum lipids, and a decrease in serum insulin and HOMA-B were observed in the diabetic group, effects that reversed following pioglitazone and SCE treatment. The diabetic group showed a downregulation of GLUT-۴ expression in skeletal muscle while an increase was observed in adipose tissue. Conclusion: A high-fat diet and low dose streptozotocin-induced experimental T۲DM model of insulin resistance was developed to screen novel insulin sensitizers. Data generated demonstrated that altered GLUT-۴ levels could be used as a biomarker of insulin resistance. Antidiabetic activity of S. cumini hydro-ethanolic seed extract was also confirmed in this study.