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

Beall, C., Watterson, K. R., McCrimmon, R. J. and Ashford, M. L.J. (2013) AMPK modulates glucose-sensing in insulin-secreting cells by altered phosphotransfer to KATP channels. Journal of Bioenergetics and Biomembranes, 45(3), pp. 229-241. (doi: 10.1007/s10863-013-9509-9) (PMID:23575945)

Abstract

Glucose-sensing (GS) behaviour in pancreatic β-cells is dependent on ATP-sensitive K(+) channel (KATP) activity, which is controlled by the relative levels of the KATP ligands ATP and ADP, responsible for closing and opening KATP, respectively. However, the mechanism by which β-cells transfer energy status from mitochondria to KATP, 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 KATP 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 AP5A blocked this action of AMPK. Using conditions that maximised AMPK-induced KATP opening, there was a significant increase in AK1, AK2 and UCP2 mRNA expression. Thus we propose that KATP 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 KATP by phosphotransfer cascades.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Watterson, Dr Kenneth
• Authors: Beall, C., Watterson, K. R., McCrimmon, R. J., and Ashford, M. L.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Journal of Bioenergetics and Biomembranes
• Publisher: Springer
• ISSN: 0145-479X
• ISSN (Online): 1573-6881
• Published Online: 11 April 2013
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in Journal of Bioenergetics and Biomembranes 45(3):229-241
• Publisher Policy: Reproduced under a Creative Commons License