Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db Mice.

ABSTRACT: Recent evidence supported the presence of a local renin-angiotensin system (RAS) in the pancreas, which is implicated in many physiological and pathophysiological processes. We utilized small interfering RNA (siRNA) to investigate the effects of angiotensin II type 1 receptor (AT1R) knockdown on glucose-stimulated insulin secretion (GSIS) in isolated islets of db/db mice and to explore the potential mechanisms involved. We found that Ad-siAT1R treatment resulted in a significant decrease both in AT1R mRNA level and in AT1R protein expression level. With downexpression of AT1R, notable increased insulin secretion and decreased glucagon secretion levels were found by perifusion. Simultaneously, significant increased protein levels of IRS-1 (by 85%), IRS-2 (by 95%), PI3K(85) (by 112.5%), and

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC3859026 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature