Effect of small interfering RNA-mediated angiotensin II type 1 receptor knockdown on first-phase insulin secretion in isolated diabetic rat islets / 南方医科大学学报
Journal of Southern Medical University
;
(12): 671-676, 2015.
Article
in Chinese
| WPRIM
| ID: wpr-355306
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Islets of Langerhans
/
Protein Serine-Threonine Kinases
/
Bodily Secretions
/
RNA, Small Interfering
/
Angiotensin II Type 1 Receptor Blockers
/
Diabetes Mellitus, Experimental
/
Glucose Transporter Type 2
/
Gene Knockdown Techniques
/
Glucose
Limits:
Animals
Language:
Chinese
Journal:
Journal of Southern Medical University
Year:
2015
Type:
Article
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