Hypothalamic glucagon signals through the KATP channels to regulate glucose production.

ABSTRACT: Insulin, leptin and GLP-1 signal in the mediobasal hypothalamus (MBH) to lower hepatic glucose production (GP). MBH glucagon action also inhibits GP but the downstream signaling mediators remain largely unknown. In parallel, a lipid-sensing pathway involving MBH AMPK?malonyl-CoA?CPT-1?LCFA-CoA?PKC-? leading to the activation of KATP channels lowers GP. Given that glucagon signals through the MBH PKA to lower GP, and PKA inhibits AMPK in hypothalamic cell lines, a possibility arises that MBH glucagon-PKA inhibits AMPK, elevates LCFA-CoA levels to activate PKC-?, and activates KATP channels to lower GP. We here report that neither molecular or chemical activation of MBH AMPK nor inhibition of PKC-? negated the effect of MBH glucagon. In contrast, molecular and chemical inhibition of MBH KATP channels negated MBH glucagon's effect to lower GP. Thus, MBH glucagon signals through a lipid-sensing independent but KATP channel-dependent pathway to regulate GP.

SUBMITTER: Abraham MA 

PROVIDER: S-EPMC3953686 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature