کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1936181 | 1050685 | 2008 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Cytosolic adenylate kinases regulate K-ATP channel activity in human β-cells Cytosolic adenylate kinases regulate K-ATP channel activity in human β-cells](/preview/png/1936181.png)
The role of adenylate kinase (AK) as a determinant of K-ATP channel activity in human pancreatic β-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 β-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.
Journal: Biochemical and Biophysical Research Communications - Volume 368, Issue 3, 11 April 2008, Pages 614–619