GPRC6A is a Potential Therapeutic Target for Metformin Regulation of Glucose Homeostasis in Mice.

ABSTRACT: Understanding the mechanism of metformin actions in treating type 2 diabetes is limited by an incomplete knowledge of the specific protein targets mediating its metabolic effects. Metformin has structural similarities to L-Arginine (2-amino-5-guanidinopentanoic acid), which is a ligand for GPRC6A, a Family C G-protein coupled receptor that regulates energy metabolism. Ligand activation of GPRC6A results in lowering of blood glucose and other metabolic changes resembling the therapeutic effect of metformin. In the current study, we tested if metformin activates GPRC6A. We used Alphafold2 to develop a structural model for L-Arginine (L-Arg) binding to the extracellu-lar bilobed venus flytrap domain (VFT) of GPRC6A. We found that metformin docked to the site in the VFT that overlaps the bindi

SUBMITTER: Pi M 

PROVIDER: S-EPMC11370357 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature