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 different small-molecule AMPK activators, we briefly review the various mechanisms for controlling hepatic glucose production, mainly via gluconeogenesis. The different experimental 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.
In this issue Arora and colleagues (pp. 25–39) show that Plasmodium PfUSP is an essential protease for parasite survival, and its inhibition increases the efficacy of artemisinin-based drugs. Therefore, PfUSP can be targeted to develop novel scaffolds for developing new antimalarials to combat artemisinin resistance. The cover image shows fluorescent microscope images of PfUSP transgenic parasites immuno-stained with anti-HA and anti-BiP antibody at different time points in control and iKD sets. This depicts the effect of down-regulation of PfUSP on development of parasite endoplasmic reticulum. The image is courtesy of Asif Mohmmed.
AMPK inhibits liver gluconeogenesis: fact or fiction?
Manuel Johanns, Louis Hue, Mark H. Rider; AMPK inhibits liver gluconeogenesis: fact or fiction?. Biochem J 13 January 2023; 480 (1): 105–125. doi: https://doi.org/10.1042/BCJ20220582
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