[HTML][HTML] The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity

B Viollet, F Andreelli, SB Jørgensen… - The Journal of …, 2003 - Am Soc Clin Investig
B Viollet, F Andreelli, SB Jørgensen, C Perrin, A Geloen, D Flamez, J Mu, C Lenzner…
The Journal of clinical investigation, 2003Am Soc Clin Investig
AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid
metabolism. To better understand the physiological role of AMPK, we generated a knockout
mouse model in which the AMPKα2 catalytic subunit gene was inactivated. AMPKα2–/–mice
presented high glucose levels in the fed period and during an oral glucose challenge
associated with low insulin plasma levels. However, in isolated AMPKα2–/–pancreatic islets,
glucose-and l-arginine–stimulated insulin secretion were not affected. AMPKα2–/–mice …
AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKα2 catalytic subunit gene was inactivated. AMPKα2–/– mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKα2–/– pancreatic islets, glucose- and L-arginine–stimulated insulin secretion were not affected. AMPKα2–/– mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKα2–/– muscles. These data indicate that AMPKα2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKα2–/– mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKα2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity.
The Journal of Clinical Investigation