Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Angiotensin II exerts glucose-dependent effects on Kv currents in mouse pancreatic β-cells via angiotensin II type 2 receptors

Angiotensin II exerts glucose-dependent effects on Kv currents in mouse pancreatic β-cells via... Abstract Hyperglycemia-associated glucotoxicity induces β-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 β-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 β-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. β-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 β-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 β-cell function through modification of the K v channel which may be associated with the RAS. renin-angiotensin system electrophysiology K v 2.1 channel losartan PD123319 insulin secretion Copyright © 2010 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Cell Physiology The American Physiological Society

Angiotensin II exerts glucose-dependent effects on Kv currents in mouse pancreatic β-cells via angiotensin II type 2 receptors

Loading next page...
 
/lp/the-american-physiological-society/angiotensin-ii-exerts-glucose-dependent-effects-on-kv-currents-in-GkSDZtdxZ0

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
The American Physiological Society
Copyright
Copyright © 2010 the American Physiological Society
ISSN
0363-6143
eISSN
1522-1563
DOI
10.1152/ajpcell.00575.2008
pmid
19889960
Publisher site
See Article on Publisher Site

Abstract

Abstract Hyperglycemia-associated glucotoxicity induces β-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 β-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 β-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. β-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 β-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 β-cell function through modification of the K v channel which may be associated with the RAS. renin-angiotensin system electrophysiology K v 2.1 channel losartan PD123319 insulin secretion Copyright © 2010 the American Physiological Society

Journal

AJP - Cell PhysiologyThe American Physiological Society

Published: Feb 1, 2010

There are no references for this article.