Abstract
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-4. A defect in this step is associated with reduced glucose utilization in muscle and adipose tissue, as observed in insulin-resistant type-2 diabetes mellitus (T2DM) patients. This study aimed to develop an experimental T2DM model and evaluate altered glucose transporter type 4 (GLUT-4) 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 12 weeks and dosed intraperitoneally with streptozotocin (35 mg/kg). After treatment for 21 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-4 expression in skeletal muscle while an increase was observed in adipose tissue. Conclusion: A high-fat diet and low dose streptozotocin-induced experimental T2DM model of insulin resistance was developed to screen novel insulin sensitizers. Data generated demonstrated that altered GLUT-4 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.
Highlights
The principal mechanism responsible for reducing blood glucose is through insulin-stimulated glucose transport into skeletal muscle
Type-2 diabetes mellitus (T2DM) patients suffer from a dual-pronged effect of both impaired insulin secretion from pancreatic beta cells and insulin resistance (IR)
We observed a significant increase in fasting blood glucose, a decrease in beta-cell dysfunction, an increase in IR, an elevation in plasma lipids and a decreased glucose transporter type 4 (GLUT-4) expression in diaphragm muscle of the diabetic rats as compared to the normal rats
Summary
The principal mechanism responsible for reducing blood glucose is through insulin-stimulated glucose transport into skeletal muscle. A defect in this step is associated with reduced glucose utilization in muscle and adipose tissue, as observed in insulin-resistant type-2 diabetes mellitus (T2DM) patients. This study aimed to develop an experimental T2DM model and evaluate altered glucose transporter type 4 (GLUT-4) levels as a biomarker of insulin resistance. Type-2 diabetes mellitus (T2DM) patients suffer from a dual-pronged effect of both impaired insulin secretion from pancreatic beta cells and insulin resistance (IR). Glucose transport into skeletal muscle through GLUT-4 is considered an important step for whole-body glucose uptake. This has a primary role in IR in T2DM [3]. GLUT-4 translocates itself to the cell membrane and mediates insulin stimulated glucose transport by activating the phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (P-AKT) pathway [4]
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