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Diabetologia. 2005 Jun;48(6):1159-67. Epub 2005 May 5.

Angiotensin II type 1 receptor inhibition markedly improves the blood perfusion, oxygen tension and first phase of glucose-stimulated insulin secretion in revascularised syngeneic mouse islet grafts.

Author information

1
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.

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.

PMID:
15877216
DOI:
10.1007/s00125-005-1761-z
[Indexed for MEDLINE]

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