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

Biochem Biophys Res Commun. 2008 Apr 11;368(3):614-9. doi: 10.1016/j.bbrc.2008.01.109. Epub 2008 Feb 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism*
  • Adenylyl Cyclases / metabolism
  • Animals
  • Cell Line
  • Cytosol / metabolism
  • Glucose / metabolism*
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Ion Channel Gating / physiology*
  • Isoenzymes / metabolism*
  • Potassium Channels / metabolism*
  • Rats


  • Insulin
  • Isoenzymes
  • Potassium Channels
  • mitochondrial K(ATP) channel
  • Adenylate Kinase
  • adenylate kinase 1
  • adenylate kinase 5
  • Adenylyl Cyclases
  • Glucose