First Author | Song WJ | Year | 2011 |
Journal | Cell Metab | Volume | 13 |
Issue | 3 | Pages | 308-19 |
PubMed ID | 21356520 | Mgi Jnum | J:172258 |
Mgi Id | MGI:5005049 | Doi | 10.1016/j.cmet.2011.02.002 |
Citation | Song WJ, et al. (2011) Snapin mediates incretin action and augments glucose-dependent insulin secretion. Cell Metab 13(3):308-19 |
abstractText | Impaired insulin secretion contributes to the pathogenesis of type 2 diabetes mellitus (T2DM). Treatment with the incretin hormone glucagon-like peptide-1 (GLP-1) potentiates insulin secretion and improves metabolic control in humans with T2DM. GLP-1 receptor-mediated signaling leading to insulin secretion occurs via cyclic AMP stimulated protein kinase A (PKA)- as well as guanine nucleotide exchange factor-mediated pathways. However, how these two pathways integrate and coordinate insulin secretion remains poorly understood. Here we show that these incretin-stimulated pathways converge at the level of snapin, and that PKA-dependent phosphorylation of snapin increases interaction among insulin secretory vesicle-associated proteins, thereby potentiating glucose-stimulated insulin secretion (GSIS). In diabetic islets with impaired GSIS, snapin phosphorylation is reduced, and expression of a snapin mutant, which mimics site-specific phosphorylation, restores GSIS. Thus, snapin is a critical node in GSIS regulation and provides a potential therapeutic target to improve beta cell function in T2DM. |