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Glucose Deprivation Regulates K(ATP) Channel Trafficking via, AMP-Activated Protein Kinase in Pancreatic beta-Cells

Cited 60 time in Web of Science Cited 65 time in Scopus
Authors
Lim, Ajin; Park, Sun-Hyun; Sohn, Jong-Woo; Jeon, Ju-Hong; Ho, Won-Kyung; Lee, Suk-Ho; Song, Dae-Kyu; Park, Jae-Hyung
Issue Date
2009-12
Publisher
AMER DIABETES ASSOC
Citation
DIABETES; Vol.58 12; 2813-2819
Abstract
OBJECTIVE-AMP-activated protein kinase (AMPK) and the ATP-sensitive K(+) (K(ATP)) channel are metabolic sensors that become activated during metabolic stress. AMPK is an important regulator of metabolism, whereas the K(ATP) channel is a regulator of cellular excitability. Cross talk between these systems is poorly understood. RESEARCH DESIGN AND METHODS-Rat pancreatic beta-cells or INS-1 cells were pretreated for 2 h at various concentrations of glucose. Maximum K(ATP) conductance (G(max)) was monitored by whole-cell measurements after intracellular ATP washout using ATP-free internal solutions. K(ATP) channel activity (NPo) was monitored by inside-out patch recordings in the presence of diazoxide. Distributions of K(ATP) channel proteins (Kir6.2 and SUR1) were examined using immunofluorescence imaging and surface biotinylation studies. Insulin secretion from rat pancreatic islets was measured using an enzyme immunoassay. RESULTS-G(max) and NPo in cells pretreated with glucose-free or 3 mmol/l glucose solutions were significantly higher than in cells pretreated in 11.1 mmol/l glucose solutions. Immunofluorescence imaging and biotinylation studies revealed that glucose deprivation induced an increase in the surface level of Kir6.2 without affecting the total cellular amount. Increases in G(max) and the surface level of Kir6.2 were inhibited by compound C, an AMPK inhibitor, and siAMPK transfection. The effects of glucose deprivation on K(ATP) channels were mimicked by an AMPK activator. Glucose deprivation reduced insulin secretion, but this response was attenuated by compound C. CONCLUSIONS-K(ATP) channel trafficking is regulated by energy status via AMPK, and this mechanism may play a key role in inhibiting insulin secretion under low energy status. Diabetes 58:281.3-2819, 2009
ISSN
0012-1797
Language
English
URI
https://hdl.handle.net/10371/76241
DOI
https://doi.org/10.2337/db09-0600
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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