Hepatocyte cholesterol content modulates glucagon receptor signalling.

ABSTRACT:

Objective

To determine whether glucagon receptor (GCGR) actions are modulated by cellular cholesterol levels.

Methods

We determined the effects of experimental cholesterol depletion and loading on glucagon-mediated cAMP production, ligand internalisation and glucose production in human hepatoma cells, mouse and human hepatocytes. GCGR interactions with lipid bilayers were explored using coarse-grained molecular dynamic simulations. Glucagon responsiveness was measured in mice fed a high cholesterol diet with or without simvastatin to modulate hepatocyte cholesterol content.

Results

GCGR cAMP signalling was reduced by higher cholesterol levels across different cellular models. Ex vivo glucagon-induced glucose output from mouse hepatocytes was enhanced by simvastatin tr

SUBMITTER: McGlone ER 

PROVIDER: S-EPMC9254120 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature