Glucose-dependent regulation of AMP-activated protein kinase in MIN6 beta cells is not affected by the protein kinase A pathway.

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. In pancreatic beta cells, glucose induces the dephosphorylation of Thr172 within the catalytic subunit and the inactivation of the AMPK complex. Here we demonstrate that glucose also activates protein kinase A (PKA), leading to the phosphorylation of AMPKα at Ser485 and Ser497. However, these modifications do not impair the phosphorylation of Thr172 by upstream kinases, and phosphorylation of Thr172 does not affect the phosphorylation of AMPKα by PKA either. Thus, although phosphorylation of Thr172 and Ser485/Ser497 are inversely correlated in response to glucose, they follow an independent regulation.