| First Author | Svendsen B | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 5 | Pages | 1127-1134.e2 |
| PubMed ID | 30380405 | Mgi Jnum | J:270934 |
| Mgi Id | MGI:6278343 | Doi | 10.1016/j.celrep.2018.10.018 |
| Citation | Svendsen B, et al. (2018) Insulin Secretion Depends on Intra-islet Glucagon Signaling. Cell Rep 25(5):1127-1134.e2 |
| abstractText | The intra-islet theory states that glucagon secretion is suppressed when insulin secretion is stimulated, but glucagon's role in intra-islet paracrine regulation is controversial. This study investigated intra-islet functions of glucagon in mice. We examined glucagon-induced insulin secretion using isolated perfused pancreata from wild-type, GLP-1 receptor (GLP-1R) knockout, diphtheria toxin-induced proglucagon knockdown, beta cell-specific glucagon receptor (Gcgr) knockout, and global Gcgr knockout (Gcgr(-/-)) mice. We found that glucagon stimulates insulin secretion through both Gcgr and GLP-1R. Moreover, loss of either Gcgr or GLP-1R does not change insulin responses, whereas combined blockage of both receptors significantly reduces insulin secretion. Active GLP-1 is identified in pancreatic perfusate from Gcgr(-/-) but not wild-type mice, suggesting that beta cell GLP-1R activation results predominantly from glucagon action. Our results suggest that combined activity of glucagon and GLP-1 receptors is essential for beta cell secretory responses, emphasizing a role for paracrine intra-islet glucagon actions to maintain appropriate insulin secretion. |
