Actions and interactions of AMPK with insulin, the peroxisomal-proliferator activated receptors and sirtuins

Abstract

AMP-activated protein kinase (AMPK) activity responds to a requirement to increase cellular ATP production and/or to conserve available ATP. AMPK is therefore central to the mechanisms of adjustment to fluctuating energy demand or metabolic substrate supply. AMPK has important actions in several insulin-responsive tissues, as well as in the pancreatic β cell, through which it can modulate glycemic control, insulin action and metabolic substrate selection and disposal. We review recent novel findings elucidating the mechanisms by which AMPK activation can correct impaired insulin action. However, we also emphasize not only the similarities, but also the differences in the actions of insulin and AMPK. We focus on metabolic interfaces between AMPK, peroxisomal proliferator-activated receptors, sirtuins and mTORC.

Keywords::

• AMPK
• glucose and lipid metabolism
• mammalian target-of-rapamycin complex
• peroxisomal proliferator-activated receptors
• sirtuins
• Type 2 diabetes

Financial & competing interests disclosure

The authors’ work cited in this review was supported by funding from Diabetes UK (RD01/2249, RD 04/2863, BDA:RD07/0003568, BDA:RD08/3665) to MC Sugden and MJ Holness. MFP Silvestre is funded by a grant from the Fundação para a Ciência e a Tecnologia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.