Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 368, Issue 3, Pages 614-619Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.01.109
Keywords
adenylate kinase; K-ATP channel; diadenosine pentaphosphate; expression; glucose; beta-cell; Islet
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Funding
- NIDDK NIH HHS [R01 DK045817-13, R01 DK045817-14, R01 DK045817, R01 DK069575] Funding Source: Medline
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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. (c) 2008 Published by Elsevier Inc.
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