Angiotensin II type 1 receptor inhibition markedly improves the blood perfusion, oxygen tension and first phase of glucose-stimulated insulin secretion ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-06

AUTHORS

C. Kampf, T. Lau, R. Olsson, P. S. Leung, P.-O. Carlsson

ABSTRACT

AIMS/HYPOTHESIS: We recently found evidence of an angiotensin-generating system in pancreatic islets. The present study investigated the effect of endogenously produced angiotensin II on microcirculation and function in transplanted islets. MATERIALS AND METHODS: Losartan, an angiotensin II type 1 receptor inhibitor, was administered either acute intravenously to mice with 4-week-old islet renal subcapsular transplants, or added to the drinking water for the final 14 days or throughout the 4-week post-transplantation period. The graft-bearing kidney was, in some cases, dissected out and perfused in vitro to evaluate the effect of angiotensin II and losartan on glucose-stimulated insulin release from the grafts. RESULTS: Losartan treatment throughout the 4-week post-transplantation period had negative effects on islet revascularisation as well as on islet graft insulin release. However, administration of losartan, either intravenously or orally, after the formation of a new vascular network, improved islet graft blood perfusion. PO2 in the islet transplants was also effectively improved by the losartan treatment. Graft perfusion experiments showed a markedly better first phase of glucose-stimulated insulin release in transplanted islets when exposed to losartan. In contrast, acute administration of angiotensin II decreased islet graft blood flow, PO2 and glucose-stimulated insulin release. CONCLUSIONS/INTERPRETATION: This study shows that inhibition of the islet reninangiotensin system may be a feasible strategy to increase the blood perfusion, PO2 and function within islet grafts. Such treatment should not be initiated, however, before the islet vascular system has been formed. More... »

PAGES

1159-1167

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00125-005-1761-z

DOI

http://dx.doi.org/10.1007/s00125-005-1761-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041202829

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15877216


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