Effects of Hydrogen Sulfide on Carbohydrate Metabolism in Obese Type 2 Diabetic Rats.

Sevda Gheibi,Asghar Ghasemi,Sajad Jeddi,Khosrow Kashfi

doi:10.3390/molecules24010190

Abstract

Hydrogen sulfide (H2S) is involved in the pathophysiology of type 2 diabetes. Inhibition and stimulation of H2S synthesis has been suggested to be a potential therapeutic approach for type 2 diabetes. The aim of this study was therefore to determine the effects of long-term sodium hydrosulfide (NaSH) administration as a H2S releasing agent on carbohydrate metabolism in type 2 diabetic rats. Type 2 diabetes was established using high fat-low dose streptozotocin. Rats were treated for 9 weeks with intraperitoneal injections of NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg). Serum glucose was measured weekly for one month and then at the end of the study. Serum insulin was measured before and after the treatment. At the end of the study, glucose tolerance, pyruvate tolerance and insulin secretion were determined and blood pressure was measured. In diabetic rats NaSH at 1.6–5.6 mg/kg increased serum glucose (11%, 28%, and 51%, respectively) and decreased serum insulin, glucose tolerance, pyruvate tolerance and in vivo insulin secretion. In controls, NaSH only at 5.6 mg/kg increased serum glucose and decreased glucose tolerance, pyruvate tolerance and insulin secretion. Chronic administration of NaSH in particular at high doses impaired carbohydrate metabolism in type 2 diabetic rats.

Highlights

Hydrogen sulfide (H2 S), a novel gasotransmitter, is involved in manyphysiological processes [1]
KATP channels play a key role in insulin secretion in pancreatic β-cells [3], where opening of the channels by H2 S
In Zucker diabetic fatty rats, the rate of endogenous H2 S production is higher than non-diabetic rats and inhibition of H2 S production restores hyperglycemia to near normal levels [7]

Summary

Introduction

Hydrogen sulfide (H2 S), a novel gasotransmitter, is involved in many (patho)physiological processes [1]. ATP-sensitive potassium channels (KATP ) in vascular smooth muscle cells [2]. KATP channels play a key role in insulin secretion in pancreatic β-cells [3], where opening of the channels by H2 S decreases insulin secretion [4]. Both endogenous and exogenous H2 S inhibit insulin secretion from β-cells by activation of KATP channels and inhibition of L-type voltage-dependent calcium channels [5]. Through inhibition of glucose transporter-4 (GLUT-4), H2 S inhibits insulin-stimulated glucose uptake in white adipocytes in rat, indicating that H2 S decreases insulin sensitivity of adipocytes [6]. In Zucker diabetic fatty rats, the rate of endogenous H2 S production is higher than non-diabetic rats and inhibition of H2 S production restores hyperglycemia to near normal levels [7]

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Methods

Conclusion