Abstract
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, β 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 β cell GLP-1R activation results predominantly from glucagon action. Our results suggest that combined activity of glucagon and GLP-1 receptors is essential for β cell secretory responses, emphasizing a role for paracrine intra-islet glucagon actions to maintain appropriate insulin secretion. Glucose-stimulated insulin secretion can be regulated by glucagon and GLP-1 receptors on paracrine β-cells. Svendsen et al. find that complete blockade of glucagon signaling in islets severely limits insulin secretion but establish that paracrine glucagon signaling involves both the glucagon and GLP-1 receptors.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cell Reports |
| Vol/bind | 25 |
| Udgave nummer | 5 |
| Sider (fra-til) | 1127-1134.E2 |
| ISSN | 2211-1247 |
| DOI | |
| Status | Udgivet - 2018 |