Expression and hypoxic regulation of the endothelin system in endocrine cells of human and rat pancreatic islets

Kugelmeier, Patrick; Nett, Philipp C; Züllig, Richard; Lehmann, Roger; Weber, Markus; Moritz, Wolfgang (2008). Expression and hypoxic regulation of the endothelin system in endocrine cells of human and rat pancreatic islets. Journal of the pancreas JOP, 9(2), pp. 133-49. Genova: E.S. Burioni ricerche bibliografiche

Full text not available from this repository. (Request a copy)

CONTEXT: The success of pancreatic islet transplantation depends largely on the capacity of the islet graft to survive the initial phase immediately after transplantation until revascularization is completed. Endothelin-1 (ET-1) is a strong vasoconstrictor which has been involved in solid organ graft failure but is also known to be a potent mitogenic/anti-apoptotic factor which could also potentially enhance the survival of the transplanted islets. OBJECTIVE: Characterization of the endothelin system with regard to a potential endothelin agonist/antagonist treatment. DESIGN: Regulated expression of the endothelin system in human and rat pancreatic islets and beta-cell lines was assessed by means of immunohistochemistry, competition binding studies, western blot, RT-PCR, real-time PCR and transplant studies. RESULTS: ET-1, ETA- and ETB-receptor immunoreactivity was identified in the endocrine cells of human and rat pancreatic islets. The corresponding mRNA was detectable in rat beta-cell lines and isolated rat and human pancreatic islets. Competition binding studies on rat islets revealed binding sites for both receptor types. ET-1 stimulated the phosphorylation of mitogen-activated protein kinase, which was prevented by ETA- and ETB-receptor antagonists. After exposure to hypoxia equal to post-transplant environment oxygen tension, mRNA levels of ET-1 and ETB-receptor of human islets were robustly induced whereas ETA-receptor mRNA did not show significant changes. Immunostaining signals for ET-1 and ETA-receptor of transplanted rat islets were markedly decreased when compared to native pancreatic sections. CONCLUSIONS: In pancreatic islets, ET-1 and its receptors are differentially expressed by hypoxia and after transplantation. Our results provide the biological basis for the study of the potential use of endothelin agonists/antagonists to improve islet transplantation outcome.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
UniBE Contributor:	Nett, Philipp C.
ISSN:	1590-8577
ISBN:	18326921
Publisher:	E.S. Burioni ricerche bibliografiche
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:05
Last Modified:	05 Dec 2022 14:20
PubMed ID:	18326921
URI:	https://boris.unibe.ch/id/eprint/28479 (FactScience: 120948)