Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 440, Issue 4, Pages 539-544Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.09.099
Keywords
PTEN; Leptin; AMPK; GSK3 beta; K-ATP channel; Pancreatic beta-cell
Categories
Funding
- National Research Foundation of Korea [2010-0029394]
- Ministry of Science and Future Planning
- National Research Foundation of Korea [2010-0029394] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Leptin regulates pancreatic beta-cell excitability through AMP-activated protein kinase (AMPK)-mediated ATP-sensitive potassium (K-ATP) channel trafficking. However, the signaling components connecting AMPK to K-ATP channel trafficking are not identified. In this study, we discovered that AMPK inhibits phosphatase and tensin homologue (PTEN) via glycogen synthase kinase 3 beta (GSK3 beta) and this signaling pathway is crucial for K-ATP channel trafficking in leptin-treated pancreatic beta-cells. Pharmacologic or genetic inhibition of AMPK or GSK3 beta, but not casein kinase 2 (CK2), impaired leptin-induced PTEN inactivation and thereby K-ATP channel trafficking. The PTEN mutant lacking both protein and lipid phosphatase activity is sufficient to induce K-ATP channel trafficking without leptin. These results present a novel signaling mechanism that underlies leptin regulation of K-ATP channel trafficking in pancreatic beta-cells. Our findings assist in gaining a broader perspective on the peripheral action of leptin on pancreatic beta-cell physiology and glucose homeostasis. (C) 2013 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available