| First Author | Xu W | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 5 | Pages | 112529 |
| PubMed ID | 37200193 | Mgi Jnum | J:341014 |
| Mgi Id | MGI:7487880 | Doi | 10.1016/j.celrep.2023.112529 |
| Citation | Xu W, et al. (2023) Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic beta cells. Cell Rep 42(5):112529 |
| abstractText | Male mice lacking the androgen receptor (AR) in pancreatic beta cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in beta cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male beta cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO(2), activating the HCO(3)(-)-sensitive soluble adenylate cyclase; and (2) increased Galpha(s) recruitment to GLP-1 receptor and AR complexes, activating transmembrane adenylate cyclase. Additionally, testosterone enhances GSIS in human islets via a focal adhesion kinase/SRC/phosphatidylinositol 3-kinase/mammalian target of rapamycin complex 2 actin remodeling cascade. We describe the testosterone-stimulated AR interactome, transcriptome, proteome, and metabolome that contribute to these effects. This study identifies AR genomic and non-genomic actions that enhance GLP-1-stimulated insulin exocytosis in male beta cells. |
