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J Herbmed Pharmacol. 2021;10(3): 331-338.
doi: 10.34172/jhp.2021.38
  Abstract View: 183
  PDF Download: 187

Original Article

Establishment of long-term high-fat diet and low dose streptozotocin-induced experimental type-2 diabetes mellitus model of insulin resistance and evaluation of seed extracts of Syzygium cumini

Pratibha Nadig 1* ORCID logo, Meharban Asanaliyar 1 ORCID logo, Kevin Manohar Salis 1 ORCID logo

1 Department of Pharmacology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore 560066, Karnataka, India

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.
Keywords: Insulin resistance, Glucose transporter type 4, Homeostasis model of assessment for insulin resist, Real-time polymerase chain reaction, High fat diet, Experimental diabetes
The research is relevant to public health as it involves the identification of genetic biomarkers related to the understanding of insulin resistance and developing a screening model for the identification of insulin sensitizers.
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Submitted: 01 Feb 2021
Revision: 24 Mar 2021
Accepted: 26 Mar 2021
ePublished: 02 Jul 2021
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