| First Author | Hodson DJ | Year | 2014 |
| Journal | Mol Endocrinol | Volume | 28 |
| Issue | 6 | Pages | 860-71 |
| PubMed ID | 24766140 | Mgi Jnum | J:214671 |
| Mgi Id | MGI:5603680 | Doi | 10.1210/me.2014-1038 |
| Citation | Hodson DJ, et al. (2014) Incretin-modulated beta cell energetics in intact islets of Langerhans. Mol Endocrinol 28(6):860-71 |
| abstractText | Incretins such as glucagon-like peptide 1 (GLP-1) are released from the gut and potentiate insulin release in a glucose-dependent manner. Although this action is generally believed to hinge on cAMP and protein kinase A signaling, up-regulated beta cell intermediary metabolism may also play a role in incretin-stimulated insulin secretion. By employing recombinant probes to image ATP dynamically in situ within intact mouse and human islets, we sought to clarify the role of GLP-1-modulated energetics in beta cell function. Using these techniques, we show that GLP-1 engages a metabolically coupled subnetwork of beta cells to increase cytosolic ATP levels, an action independent of prevailing energy status. We further demonstrate that the effects of GLP-1 are accompanied by alterations in the mitochondrial inner membrane potential and, at elevated glucose concentration, depend upon GLP-1 receptor-directed calcium influx through voltage-dependent calcium channels. Lastly, and highlighting critical species differences, beta cells within mouse but not human islets respond coordinately to incretin stimulation. Together, these findings suggest that GLP-1 alters beta cell intermediary metabolism to influence ATP dynamics in a species-specific manner, and this may contribute to divergent regulation of the incretin-axis in rodents and man. |
