The AMP-regulated kinase family: Enigmatic targets for diabetes therapy

Abstract

Please cite this article as: Rutter, G.A., Leclerc, I., The AMP-regulated kinase family: enigmatic targets for diabetes therapy, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Pt 1):1-16, 2003). In the subsequent five years, dramatic strides have taken place in our understanding of the role of AMPK in the control of whole body metabolic homeostasis, the regulation of the enzyme by upstream kinases, and its molecular structure.These new studies and earlier work arguably propel AMPK, and perhaps related family members into a "super league" of potential therapeutic targets for maladies including diabetes, cancer, heart disease, and obesity. Here we survey some of these recent advances, focussing on the role of this and related enzymes in the control of pancreatic β-cell function and glucose homeostasis.

Autophagy in human type 2 diabetes pancreatic beta cells

“…At the present time we can only speculate on the mechanisms leading to these effects. Metformin potentiates AMP kinase (AMPK) activity [14]. Beside several other actions, AMPK can inhibit the mammalian target of rapamycin (mTOR) [15].…”

Regulation of insulin secretion: a matter of phase control and amplitude modulation

“…1), but other messengers could also be involved [8,34,48]. Recent studies call for a (re)evaluation of the roles of cAMP [49], NADPH [48, 50, 51], citrate cycle intermediates exported to the cytosol [48, 51,52], AMP-activated protein kinase [53] and granule translocation by the cytoskeleton [18,54]. Mathematical modelling of the amplifying pathway may also help to identify the effector system [55,56].…”

Protein Kinases and Pancreatic Islet Function

“…It is a target of the glucose-lowering drugs, metformin and thiazolidinediones, which act to improve insulin sensitivity in insulin-sensitive tissues such as muscle and liver (54). However, the long term effects of these drugs on cell survival and function are less clear (53).…”