Referenced in: none

Automatically associated channels: Kir6.2

Title: Cytosolic adenylate kinases regulate K-ATP channel activity in human beta-cells.

Authors: Violeta Stanojevic, Joel F Habener, George G Holz, Colin A Leech

Journal, date & volume: Biochem. Biophys. Res. Commun., 2008 Apr 11 , 368, 614-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18243136

Abstract
The role of adenylate kinase (AK) as a determinant of K-ATP channel activity in human pancreatic beta-cells was investigated. We have identified that two cytosolic isoforms of AK, AK1 and AK5 are expressed in human islets and INS-1 cells. Elevated concentrations of glucose inhibit AK1 expression and AK1 immunoprecipitates with the Kir6.2 subunit of K-ATP. AK activation by ATP+AMP stimulates K-ATP channel activity and this stimulation is abolished by AK inhibitors. We propose that glucose stimulation of beta-cells inhibits AK through glycolysis and also through the elevation of diadenosine polyphosphate levels. Glucose-dependent inhibition of AK increases the ATP/ADP ratio in the microenvironment of the K-ATP channel promoting channel closure and insulin secretion. The down-regulation of AK1 expression by hyperglycemia may contribute to the defective coupling of glucose metabolism to K-ATP channel activity in type 2 diabetes.