AMPK inhibits liver gluconeogenesis: fact or fiction?

Is there a role for AMPK in the control of hepatic gluconeogenesis and could targeting AMPK in liver be a viable strategy for treating type 2 diabetes? These are frequently asked questions this review tries to answer. After describing properties of AMPK and dif-ferent small-molecule AMPK activators, we briefly review the various mechanisms for controlling hepatic glucose production, mainly via gluconeogenesis. The different experi-mental and genetic models that have been used to draw conclusions about the role of AMPK in the control of liver gluconeogenesis are critically discussed. The effects of several anti-diabetic drugs, particularly metformin, on hepatic gluconeogenesis are also considered. We conclude that the main effect of AMPK activation pertinent to the control of hepatic gluconeogenesis is to antagonize glucagon signalling in the short-term and, in the long-term, to improve insulin sensitivity by reducing hepatic lipid content.

Automated summary

This review addresses the role of AMPK in the control of hepatic gluconeogenesis and explores the potential of targeting AMPK as a strategy for treating type 2 diabetes. The properties of AMPK and different small-molecule AMPK activators are described, and various mechanisms for controlling hepatic glucose production are reviewed. Experimental and genetic models used to investigate the role of AMPK in liver gluconeogenesis are critically discussed. The effects of anti-diabetic drugs, particularly metformin, on hepatic gluconeogenesis are also considered. The main effect of AMPK activation on the control of hepatic gluconeogenesis is to inhibit glucagon signaling and improve insulin sensitivity by reducing hepatic lipid content.