| Literature DB >> 18243136 |
Violeta Stanojevic1, Joel F Habener, George G Holz, Colin A Leech.
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.Entities:
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Year: 2008 PMID： 18243136 PMCID： PMC2915763 DOI： 10.1016/j.bbrc.2008.01.109
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575