The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury.

Acute kidney injury (AKI) disrupts energy metabolism. Targeting metabolism through AMP-activated protein kinase (AMPK) may alleviate AKI. ATX-304, a pan-AMPK activator, was evaluated in C57Bl/6 mice and tubular epithelial cell (TEC) cultures.

Disrupting AMPK-Glycogen Binding in Mice Increases Carbohydrate Utilization and Reduces Exercise Capacity.

The AMP-activated protein kinase (AMPK) is a central regulator of cellular energy balance and metabolism and binds glycogen, the primary storage form of glucose in liver and skeletal muscle. The effects of disrupting whole-body AMPK-glycogen interactions on exercise capacity and substrate utilization during exercise remain unknown. We used male whole-body AMPK double knock-in (DKI) mice with chronic disruption of AMPK-glycogen binding to determine the effects of DKI mutation on exercise capacity, patterns of whole-body substrate utilization, and tissue metabolism during exercise.

An AMPKα2-specific phospho-switch controls lysosomal targeting for activation.

AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) are metabolic kinases that co-ordinate nutrient supply with cell growth. AMPK negatively regulates mTORC1, and mTORC1 reciprocally phosphorylates S345/7 in both AMPK α-isoforms. We report that genetic or torin1-induced loss of α2-S345 phosphorylation relieves suppression of AMPK signaling; however, the regulatory effect does not translate to α1-S347 in HEK293T or MEF cells.

Mice with Whole-Body Disruption of AMPK-Glycogen Binding Have Increased Adiposity, Reduced Fat Oxidation and Altered Tissue Glycogen Dynamics.

The AMP-activated protein kinase (AMPK), a central regulator of cellular energy balance and metabolism, binds glycogen via its β subunit. However, the physiological effects of disrupting AMPK-glycogen interactions remain incompletely understood. To chronically disrupt AMPK-glycogen binding, AMPK β double knock-in (DKI) mice were generated with mutations in residues critical for glycogen binding in both the β1 (W100A) and β2 (W98A) subunit isoforms.