Involvement of amylin B-H2S-connexin 43 signaling pathway in vascular dysfunction and enhanced ischemia-reperfusion-induced myocardial injury in diabetic rats.

Xiaoyong Liu,Rui Yang,Wenwei Bai,Hu Li,Qishi Yang,Xiang Xu,Yingzheng Hao,Feng Bi

doi:10.1042/bsr20194154

Xiaoyong Liu, Rui Yang + Show 6 more

Open Access

https://doi.org/10.1042/bsr20194154

Copy DOI

Journal: Bioscience reports	Publication Date: Jun 8, 2020
Citations: 3	License type: CC BY 4.0

Affiliation: Kunming Medical University

Abstract

The present study was designed to investigate the role of amylin, H2S, and connexin 43 in vascular dysfunction and enhanced ischemia–reperfusion (I/R)-induced myocardial injury in diabetic rats. A single dose of streptozotocin (65 mg/kg) was employed to induce diabetes mellitus. After 8 weeks, there was a significant decrease in the plasma levels of amylin, an increase in I/R injury to isolated hearts (increase in CK-MB and cardiac troponin release) on the Langendorff apparatus. Moreover, there was a significant impairment in vascular endothelium function as assessed by quantifying acetylcholine-induced relaxation in norepinephrine-precontracted mesenteric arteries. There was also a marked decrease in the expression of H2S and connexin 43 in the hearts following I/R injury in diabetic rats. Treatment with amylin agonist, pramlintide (100 and 200 µg/kg), and H2S donor, NaHS (10 and 20 μmol/kg) for 2 weeks improved the vascular endothelium function, abolished enhanced myocardial injury and restored the levels of H2S along with connexin 43 in diabetic animals. However, pramlintide and NaHS failed to produce these effects the presence of gap junction blocker, carbenoxolone (20 and 40 mg/kg). Carbenoxolone also abolished the myocardial levels of connexin 43 without affecting the plasma levels of amylin and myocardial levels of H2S. The decrease in the amylin levels with a consequent reduction in H2S and connexin 43 may contribute to inducing vascular dysfunction and enhancing I/R-induced myocardial injury in diabetic rats.

Highlights

Diabetes mellitus is a metabolic disorder, which is characterized primarily by a disturbance in glucose metabolism
In non-diabetic rats, 30 min of global ischemia and 120 min of reperfusion led to myocardial injury as assessed by a significant increase in the levels of cardiac troponin T (cTnT) (Figure 1) and creatine kinase (CK-MB) (Figure 2) in the coronary perfusate collected during the reperfusion phase in comparison with corresponding basal levels
The extent of CK-MB and cTnT release was more significant from the hearts of diabetic rats in comparison with non-diabetic rats suggesting that the extent of myocardial injury was increased during the state of diabetes mellitus

Summary

Introduction

Diabetes mellitus is a metabolic disorder, which is characterized primarily by a disturbance in glucose metabolism. There have been studies showing that long-standing diabetes enhances the extent of myocardial injury in response to ischemia–reperfusion [2]. The mortality rate of myocardial infarction patients suffering from diabetes mellitus is about 2–4 times higher in comparison with non-diabetic patients [3,4]. There a need for identifying the mechanisms responsible for the enhancement in the myocardial injury during the diabetic state, and this may eventually help in the effective management of myocardial infarction in diabetic patients. Amylin is a 37 amino acid peptide hormone, which is secreted along with insulin from the pancreas to regulate the glucose levels [5,6]. Hyperinsulinemia, usually associated with type II diabetes, is associated with an increase in plasma amylin levels (hyperamylinemia) in diabetic patients [7,8].

Methods

Results

Discussion

Conclusion