AMPK regulates K(ATP) channel trafficking via PTEN inhibition in leptin-treated pancreatic ß-cells.
Park, Sun-Hyun Ho, Won-Kyung Jeon, Ju-Hong
||Park SH, etal., Biochem Biophys Res Commun. 2013 Nov 1;440(4):539-44. doi: 10.1016/j.bbrc.2013.09.099. Epub 2013 Oct 5.
||(View Article at PubMed) PMID:24103758
Leptin regulates pancreatic ß-cell excitability through AMP-activated protein kinase (AMPK)-mediated ATP-sensitive potassium (KATP) channel trafficking. However, the signaling components connecting AMPK to KATP channel trafficking are not identified. In this study, we discovered that AMPK inhibits phosphatase and tensin homologue (PTEN) via glycogen synthase kinase 3ß (GSK3ß) and this signaling pathway is crucial for KATP channel trafficking in leptin-treated pancreatic ß-cells. Pharmacologic or genetic inhibition of AMPK or GSK3ß, but not casein kinase 2 (CK2), impaired leptin-induced PTEN inactivation and thereby KATP channel trafficking. The PTEN mutant lacking both protein and lipid phosphatase activity is sufficient to induce KATP channel trafficking without leptin. These results present a novel signaling mechanism that underlies leptin regulation of KATP channel trafficking in pancreatic ß-cells. Our findings assist in gaining a broader perspective on the peripheral action of leptin on pancreatic ß-cell physiology and glucose homeostasis.