A-769662 inhibits adipocyte glucose uptake in an AMPK-independent manner

Activation of AMP-activated protein kinase (AMPK) is considered a valid strategy for the treatment type 2 diabetes. However, despite importance adipose tissue whole-body energy homeostasis, effect AMPK activation in adipocytes has only been studied to limited extent and mainly with AMP-mimetic 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), which specificity. The aim this study was evaluate allosteric activators A-769662 991 on glucose uptake adipocytes. For purpose, primary rat or human adipocytes, cultured 3T3-L1 were treated either activators, AICAR, basal insulin-stimulated assessed. Additionally, phosphorylation Akt substrate 160 kDa Furthermore, from ADaM site binding drug-resistant AMPKβ1 S108A knock-in mice employed investigate specificity drugs observed effects. Our results show that adipocyte significantly reduced by but not 991, yet neither activator had any clear effects Akt/AS160 signaling. use mutant-expressing revealed inhibition most likely AMPK-independent, finding supported rapid inhibitory exerts These data suggest per se does inhibit AICAR are AMPK-independent.