Angiotensin II type 1 receptor antagonists prevent glucose‐induced increases in islet blood flow in rats

Abstract

Objective. Renin‐angiotensin system inhibitors are reported to be beneficial in delaying the onset of diabetes mellitus. Since islet blood hyperperfusion during hyperglycaemia may be detrimental to endothelium in pancreatic islets and eventually lead to β‐cell dysfunction, we studied acute and chronic effects of angiotensin II type 1 receptor blockers (ARB) on islet blood flow before and after glucose load. Material and methods. Islet blood flow was measured using the colour microsphere method in anaesthetized Sprague‐Dawley rats before and 3 min after glucose injection. Results. Olmesartan significantly reduced blood pressure, but did not affect islet blood flow 10 min after its injection. However, pretreatment with olmesartan blunted the glucose‐induced increase in islet blood flow (62 % of control). In rats treated with olmesartan or candesartan for 4 weeks, islet blood flow was not different from untreated control, whereas the glucose‐induced increase in islet blood flow was significantly suppressed in chronically ARB‐treated rats (olmesartan 59 % of control, candesartan 64 % of control, respectively). Acute or chronic treatment with ARB did not change insulin secretion before and in response to glucose load. Pancreatic or duodenal blood flow was not affected by ARB treatment, although acute olmesartan administration reduced pancreatic blood flow after glucose load. Conclusion. ARB appears to suppress the hyperglycaemia‐induced islet hyperperfusion, which may ameliorate haemodynamic stress in pancreatic islets.

• Candesartan
• diabetes mellitus
• insulin
• microangiopathy
• microsphere
• olmesartan
• pancreas

Acknowledgements

This work was supported in part by a Grant‐in‐Aid for Scientific Research (no. 18590993. 2007) from the Ministry of Education, Science, Sports and Culture. We are grateful to K. Sekioka and J. Ishimatsu for excellent technical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.