HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chu, K. Y. Articles by Leung, P. S. PubMed PubMed Citation Articles by Chu, K. Y. Articles by Leung, P. S.

Research Article

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

¹Chinese University of Hong Kong ²The Chinese University of Hong Kong ³University of Queensland

Submitted 5 November 2008 ; revised 13 October 2009 ; accepted in final form 29 October 2009

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 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_v2.1 expression and K_v current amplitude. Enhanced expression of Ang II type 1 receptor (AT1R) was also observed under high glucose conditions whereas blockade of AT1R 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 (AT2R) 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; angiotensin II type 2 receptor; electrophysiology; Kv2.1 channel