AMPK regulates K-ATP channel trafficking via PTEN inhibition in leptin-treated pancreatic beta-cells

作者：Park Sun Hyun; Ho Won Kyung^*; Jeon Ju Hong

来源：Biochemical and Biophysical Research Communications, 2013, 440(4): 539-544.

DOI：10.1016/j.bbrc.2013.09.099

• PTEN
• Leptin
• AMPK
• GSK3 beta
• K-ATP channel
• Pancreatic beta-cell

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.

• 出版日期2013-11-1