Effect of small interfering RNA-mediated angiotensin II type 1 receptor knockdown on first-phase insulin secretion in isolated diabetic rat islets
YI Qiuyan
LIU Yanqing
ZHANG Zhen
LIU Chunyan
LU Bin
SHAO Jiaqing
Abstract：Objective To investigate the effects of angiotensin II type 1 receptor (AT1R) knockdown on the first-phase insulin secretion in isolated islets of db/db mice and explore the possible mechanisms. Methods Islets were isolated from db/db and db/m mice and the expression level of AT1R in the islets was assayed. A recombinant adenovirus containing siRNA targeting AT1R (Ad-siAT1R) and a recombinant adenovirus with nonspecific siRNA (Ad-siControl) were constructed to infect the isolated islets for 72 h. AT1R, GLUT-2, and GCK expressions in the islets were investigated and islet perifusion was performed to evaluate the kinetics of insulin release. Results The expression level of AT1R in the isolated islets from db/db mice was twice that of islets from db/m mice. The islets treated with Ad-siAT1R showed significantly decreased AT1R mRNA and protein levels and significantly increased expression of GLUT-2 (by 190%) and GCK (by 121%) compared to those treated with Ad-siControl (P<0.05). In response to stimulation with 16.7 mmol/L glucose, the first-phase insulin secretion was impaired in both Ad-siControl group and mock infected group with the peak insulin levels only 1.8 times of the basal level; the first-phase insulin secretion was markedly improved in islets treated with Ad-siAT1R, with a peak insulin level reaching 2.8 times of the basal level. Conclusions In isolated islets of db/db mice, selective AT1R inhibition can restore the first phase insulin secretion by up-regulating GLUT-2 and GCK, which may be one of the potential mechanisms by which AT1R blockers improve insulin secretion function.
Keywords：RNA interferencerennin-angiotensin systemangiotensin II type 1 receptorfirst-phase insulin secretion
Publication Date：2015-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 671-676 )