AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Reconstitution of ULK1-deficient cells with a mutant ULK2 that cannot be phosphorylated by AMPK revealed that such phosphorylation is required for mitochondrial homeostasis and cell survival during starvation.
Cellular and molecular mechanisms of metformin: an overview.
- B. Viollet, B. Guigas, Nieves Sanz Garcia, J. Leclerc, M. Foretz, F. Andreelli
- Medicine, BiologyClinical science
- 1 March 2012
Emerging new therapeutic areas for metformin will be reviewed together with recent findings from pharmacogenetic studies linking genetic variations to drug response, a promising new step towards personalized medicine in the treatment of T2D.
Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state.
It is found that in mice lacking AMPK in the liver, blood glucose levels were comparable to those in wild-type mice, and the hypoglycemic effect of metformin was maintained, demonstrating that met formin inhibits hepatic gluconeogenesis in an LKB1- and AMPK-independent manner via a decrease in hepatic energy state.
Metformin: from mechanisms of action to therapies.
AMP-Activated Protein Kinase–Deficient Mice Are Resistant to the Metabolic Effects of Resveratrol
Resveratrol increased the metabolic rate and reduced fat mass in wild-type mice but not in AMPKα1−/− mice, indicating that AMPK, which was thought to be an off-target hit of resver atrol, is the central target for the metabolic effects of res veratrol.
Biguanides suppress hepatic glucagon signaling by decreasing production of cyclic AMP
- Russell A. Miller, Q. Chu, Jianxin Xie, M. Foretz, B. Viollet, M. Birnbaum
- Biology, MedicineNature
- 19 December 2012
A novel mechanism by which metformin antagonizes the action of glucagon, thus reducing fasting glucose levels and suggesting an approach for the development of antidiabetic drugs is provided.
Mechanism of Action of A-769662, a Valuable Tool for Activation of AMP-activated Protein Kinase*
- O. Göransson, A. Mcbride, K. Sakamoto
- Biology, ChemistryJournal of Biological Chemistry
- 9 November 2007
The results show that in intact cells, the effects of A-769662 are independent of the upstream kinase utilized, and it is proposed that this direct and specific AMPK activator will be a valuable experimental tool to understand the physiological roles of AMPK.
Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth.
Metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin.
AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons.
It is suggested that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus.