Angiotensin II exerts glucose-dependent effects on K-v currents in mouse pancreatic beta-cells via angiotensin II type 2 receptors

Chu, Kwan Yi, Cheng, Qianni, Chen, Chen, Au, Lai Shan, Seto, Sai Wang, Tuo, Ya, Motin, Leonid, Kwan, Yiu Wa and Leung, Po Sing (2010) Angiotensin II exerts glucose-dependent effects on K-v currents in mouse pancreatic beta-cells via angiotensin II type 2 receptors. American Journal of Physiology - Cell Physiology, 298 2: C313-C323.


Author Chu, Kwan Yi
Cheng, Qianni
Chen, Chen
Au, Lai Shan
Seto, Sai Wang
Tuo, Ya
Motin, Leonid
Kwan, Yiu Wa
Leung, Po Sing
Title Angiotensin II exerts glucose-dependent effects on K-v currents in mouse pancreatic beta-cells via angiotensin II type 2 receptors
Journal name American Journal of Physiology - Cell Physiology   Check publisher's open access policy
ISSN 0363-6143
1522-1563
Publication date 2010-02
Year available 2009
Sub-type Article (original research)
DOI 10.1152/ajpcell.00575.2008
Volume 298
Issue 2
Start page C313
End page C323
Total pages 11
Editor Paul A. Insel
Place of publication Bethesda, MD, United States
Publisher American Physiology Society
Collection year 2010
Language eng
Subject 0601 Biochemistry and Cell Biology
920104 Diabetes
Abstract Hyper-glycemia-associated glucotoxicity induces beta-cell apoptosis but the underlying mechanisms are unknown. Interestingly, prolonged exposure to high glucose upregulates the expression and function of the renin-angiotensin system (RAS). We hypothesize that the voltage-gated outward potassium (K-v) current, which governs beta-cell membrane potential and insulin secretion, has a role in glucotoxicity. In this study, we investigated the effects of prolonged exposure to high glucose on mouse pancreatic beta-cells and concurrent effects on the RAS by examining changes in expression of angiotensin II (ANG II) receptors and changes in the expression and activity of K-v channels. beta-Cells were incubated in high glucose medium for 1-7 days and then were examined with electrophysiological and molecular biology techniques. Prolonged exposure to high glucose produced a marked increase in beta-cell primary K-v channel subunit, K(v)2.1, expression and K-v current amplitude. Enhanced expression of ANG II type 1 receptor (AT(1)R) was also observed under high glucose conditions, whereas blockade of AT(1)R by losartan did not alter K-v channel expression. External application of ANG II reduced K-v current amplitude under normal, but not high, glucose conditions. The effect of ANG II on K-v channel gating was abolished by ANG II type 2 receptor (AT(2)R) antagonism. These data suggest that hyperglycemia alters beta-cell function through modification of the K-v channel which may be associated with the RAS.
Keyword Renin-angiotensin system
Electrophysiology
K(v)2.1 channel
losartan
PD123319
Insulin secretion
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print November 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
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