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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Evaluation of Gamma Amino Butyric Acid (GABA) and Glibenclamide Combination Therapy in Streptozotocin Induced Diabetes

Author(s): Yunfeng Zhu, Sushma Devi*, Manish Kumar*, Randhir Singh Dahiya and Tarkeshwer

Volume 21, Issue 11, 2021

Published on: 07 December, 2020

Page: [2005 - 2016] Pages: 12

DOI: 10.2174/1871530320666201208110945

Abstract

Background: Type 1-diabetes (T1D) is characterized by autoimmune destruction of β-cells and loss of endogenous insulin. A lifelong dependency on exogenous supply of insulin presents a great challenge in the pharmacotherapy of T1D that elicits a quest for alternative therapies, which can protect β-cells and revive their insulinogenic functions. GABA (γ-aminobutyric acid) has immunoprotective and β-cell regenerative capabilities. Co-administration of an insulin secretagogue, such as glibenclamide (Glib), along with GABA may enhance the pancreatic insulin output in T1D.

Objective: The present study evaluated the possible mechanism of GABA in the improvement of glucose tolerance and its effects in streptozotocin (STZ) induced T1D along with Glib.

Methods: Wistar rats (180-220 g) were administered a single dose of STZ (55 mg/kg, i.p.). GABA (100 mg/kg, i.p.) and Glib (5 or 10 mg/kg, i.p.) alone or in combination were administered for 28 days. Body weight (b.w.), water consumption, fasting blood glucose (FBG), oral glucose tolerance, plasma lipids, insulin, and muscle GLUT-4 (glucose transporters) protein level were assessed.

Results: T1D significantly decreased b.w. and increased water-intake in rats. An increase in FBG and a decrease in plasma insulin and muscle GLUT-4 indicated STZ-triggered destruction of β-cells in diabetic rats accompanied with dyslipidemia. GABA or Glib (10 mg/kg) significantly improved b.w., plasma insulin and GLUT-4 levels, and ameliorated FBG and blood lipid profile in diabetic rats. GABA and Glib (5 mg/kg) combination therapy achieved far better control over hyperglycemia and related pathogenic conditions (b.w., water-intake, insulin, GLUT-4, lipids). The anti-diabetic effect of combination therapy was significantly more pronounced in comparison to individual drug treatments. Histopathological analysis revealed an increase in the number of functional pancreatic-islets by combination therapy.

Conclusion: GABA revitalized β-cells against STZ-toxicity. GABA and Glib synergistically augmented insulin secretion that can be used to manage T1D and its complications. GABA has the potential to remarkably enhance the therapeutic outcome in diabetic patients and reduce the dose of existing anti-diabetic drugs such as Glib.

Keywords: Type-1 diabetes, streptozotocin, GABA, glibenclamide, β-cell, GLUT-4.

Graphical Abstract

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