O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function

ABSTRACT: Although insulin mediated glucose uptake in skeletal muscle is a major mechanism ensuring glucose disposal in humans, glucose effectiveness, i.e., the ability of glucose itself to stimulate its own uptake independent of insulin, accounts for roughly half of the glucose disposed during an oral glucose tolerance test. Both insulin dependent and insulin independent skeletal muscle glucose uptake are however reduced in individuals with diabetes. We here show that AMPK activator O304 stimulates insulin independent glucose uptake and utilization in skeletal muscle and heart in vivo, while preventing glycogen accumulation. Combined glucose uptake and utilization requires an increased metabolic demand and we show that O304 acts as a mitochondrial uncoupler, i.e., generates a metabolic demand. O304

SUBMITTER: Norlin S 

PROVIDER: S-EPMC10457357 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature