AMPK modulates glucose-sensing in insulin-secreting cells by altered phosphotransfer to K-ATP channels

作者：Beall Craig; Watterson Kenneth R; McCrimmon Rory J; Ashford Michael L J^*

来源：Journal of Bioenergetics and Biomembranes, 2013, 45(3): 229-241.

DOI：10.1007/s10863-013-9509-9

• AMPK
• K-ATP
• Glucose
• beta-cell
• Adenylate kinase
• Creatine kinase
• UCP2

Glucose-sensing (GS) behaviour in pancreatic beta-cells is dependent on ATP-sensitive K+ channel (K-ATP) activity, which is controlled by the relative levels of the K-ATP ligands ATP and ADP, responsible for closing and opening K-ATP, respectively. However, the mechanism by which beta-cells transfer energy status from mitochondria to K-ATP,K- and hence to altered electrical excitability and insulin secretion, is presently unclear. Recent work has demonstrated a critical role for AMP-activated protein kinase (AMPK) in GS behaviour of cells. Electrophysiological recordings, coupled with measurements of gene and protein expression were made from rat insulinoma cells to investigate whether AMPK activity regulates this energy transfer process. Using the whole-cell recording configuration with sufficient intracellular ATP to keep K-ATP closed, raised AMPK activity induced GS electrical behaviour. This effect was prevented by the AMPK inhibitor, compound C and required a phosphotransfer process. Indeed, high levels of intracellular phosphocreatine or the presence of the adenylate kinase (AK) inhibitor AP(5)A blocked this action of AMPK. Using conditions that maximised AMPK-induced K-ATP opening, there was a significant increase in AK1, AK2 and UCP2 mRNA expression. Thus we propose that K-ATP opening in response to lowered glucose concentration requires AMPK activity, perhaps in concert with increased AK and UCP2 to enable mitochondrial-derived ADP signals to be transferred to plasma membrane K-ATP by phosphotransfer cascades.

• 出版日期2013-6