Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance.

ABSTRACT:

Objective

Glucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown.

Methods

Glucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot.

Results

The central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca(2+)-calmodulin-depende

SUBMITTER: Quinones M 

PROVIDER: S-EPMC4731730 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature