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. P_O2 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.