In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 298, No. 2 ( 2010-02), p. C313-C323
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.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00575.2008
Language:
English
Publisher:
American Physiological Society
Publication Date:
2010
detail.hit.zdb_id:
1477334-X
SSG:
12
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