Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 614-619 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 368 |
| Issue number | 3 |
| DOIs | |
| State | Published - Apr 11 2008 |
Keywords
- Adenylate kinase
- Diadenosine pentaphosphate
- Expression
- Glucose
- Islet
- K-ATP channel
- β-Cell
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