| First Author | de Souza AH | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 2823 |
| PubMed ID | 32071395 | Mgi Jnum | J:293454 |
| Mgi Id | MGI:6407303 | Doi | 10.1038/s41598-020-59799-2 |
| Citation | de Souza AH, et al. (2020) Intra-islet GLP-1, but not CCK, is necessary for beta-cell function in mouse and human islets. Sci Rep 10(1):2823 |
| abstractText | Glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) are gut-derived peptide hormones known to play important roles in the regulation of gastrointestinal motility and secretion, appetite, and food intake. We have previously demonstrated that both GLP-1 and CCK are produced in the endocrine pancreas of obese mice. Interestingly, while GLP-1 is well known to stimulate insulin secretion by the pancreatic beta-cells, direct evidence of CCK promoting insulin release in human islets remains to be determined. Here, we tested whether islet-derived GLP-1 or CCK is necessary for the full stimulation of insulin secretion. We confirm that mouse pancreatic islets secrete GLP-1 and CCK, but only GLP-1 acts locally within the islet to promote insulin release ex vivo. GLP-1 is exclusively produced in approximately 50% of alpha-cells in lean mouse islets and 70% of alpha-cells in human islets, suggesting a paracrine alpha to beta-cell signaling through the beta-cell GLP-1 receptor. Additionally, we provide evidence that islet CCK expression is regulated by glucose, but its receptor signaling is not required during glucose-stimulated insulin secretion (GSIS). We also see no increase in GSIS in response to CCK peptides. Importantly, all these findings were confirmed in islets from non-diabetic human donors. In summary, our data suggest no direct role for CCK in stimulating insulin secretion and highlight the critical role of intra-islet GLP-1 signaling in the regulation of human beta-cell function. |
