Header

UZH-Logo

Maintenance Infos

Endothelin inhibition delays onset of hyperglycemia and associated vascular injury in type I diabetes: Evidence for endothelin release by pancreatic islet β-cells


Ortmann, Jana; Nett, Philipp C; Celeiro, Jennifer; Traupe, Tobias; Tornillo, Luigi; Hofmann-Lehmann, Regina; Haas, Elvira; Frank, Beat; Terraciano, Luigi M; Barton, Matthias (2005). Endothelin inhibition delays onset of hyperglycemia and associated vascular injury in type I diabetes: Evidence for endothelin release by pancreatic islet β-cells. Biochemical and Biophysical Research Communications, 334(2):689-695.

Abstract

This study investigated the role of endothelin-1 for hyperglycemia, vascular, and pancreatic injury in early type I diabetes in non-obese-diabetic (NOD) mice. Endothelium dependent relaxation to acetylcholine and vascular gene expression of endothelin converting enzyme (ECE) isoforms 1 and 2 were studied as indicators of vascular injury. Endothelial NO bioactivity in the aorta was reduced in diabetic NOD mice while vascular expression of ECE-1 and ECE-2 mRNA was increased compared with controls (all p<0.05). Vascular histology was normal in all animals. Unexpectedly, treatment of prediabetic NOD mice for 6 weeks with the orally active ET(A) receptor antagonist BSF461314 prevented onset of diabetes without affecting insulitis severity. ET(A) receptor blockade also restored abnormal endothelial NO bioactivity and reduced ECE-1 and ECE-2 gene expression in NOD mice to levels comparable with healthy controls (p<0.05). Moreover, secretion of endothelin-1 in a time-dependent fashion was observed by pancreatic islet beta-cells cultured in vitro. These data suggest a critical role for ET(A) receptor signaling in the development of autoimmune forms of diabetes and the early vascular injury associated with it

Abstract

This study investigated the role of endothelin-1 for hyperglycemia, vascular, and pancreatic injury in early type I diabetes in non-obese-diabetic (NOD) mice. Endothelium dependent relaxation to acetylcholine and vascular gene expression of endothelin converting enzyme (ECE) isoforms 1 and 2 were studied as indicators of vascular injury. Endothelial NO bioactivity in the aorta was reduced in diabetic NOD mice while vascular expression of ECE-1 and ECE-2 mRNA was increased compared with controls (all p<0.05). Vascular histology was normal in all animals. Unexpectedly, treatment of prediabetic NOD mice for 6 weeks with the orally active ET(A) receptor antagonist BSF461314 prevented onset of diabetes without affecting insulitis severity. ET(A) receptor blockade also restored abnormal endothelial NO bioactivity and reduced ECE-1 and ECE-2 gene expression in NOD mice to levels comparable with healthy controls (p<0.05). Moreover, secretion of endothelin-1 in a time-dependent fashion was observed by pancreatic islet beta-cells cultured in vitro. These data suggest a critical role for ET(A) receptor signaling in the development of autoimmune forms of diabetes and the early vascular injury associated with it

Statistics

Citations

Dimensions.ai Metrics
15 citations in Web of Science®
19 citations in Scopus®
20 citations in Microsoft Academic
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 29 Nov 2016
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Department of Farm Animals
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Language:English
Date:2005
Deposited On:29 Nov 2016 11:22
Last Modified:19 Feb 2018 20:15
Publisher:Elsevier
ISSN:0006-291X
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.bbrc.2005.06.140
PubMed ID:16009335

Download