| First Author | Lee YS | Year | 2018 |
| Journal | Diabetes | Volume | 67 |
| Issue | 12 | Pages | 2601-2614 |
| PubMed ID | 30257975 | Mgi Jnum | J:267705 |
| Mgi Id | MGI:6258061 | Doi | 10.2337/db18-0155 |
| Citation | Lee YS, et al. (2018) Glucagon-Like Peptide 1 Increases beta-Cell Regeneration by Promoting alpha- to beta-Cell Transdifferentiation. Diabetes 67(12):2601-2614 |
| abstractText | Glucagon-like peptide 1 (GLP-1) can increase pancreatic beta-cells, and alpha-cells could be a source for new beta-cell generation. We investigated whether GLP-1 increases beta-cells through alpha-cell transdifferentiation. New beta-cells originating from non-beta-cells were significantly increased in recombinant adenovirus expressing GLP-1 (rAd-GLP-1)-treated RIP-CreER;R26-YFP mice. Proliferating alpha-cells were increased in islets of rAd-GLP-1-treated mice and alphaTC1 clone 9 (alphaTC1-9) cells treated with exendin-4, a GLP-1 receptor agonist. Insulin(+)glucagon(+) cells were significantly increased by rAd-GLP-1 or exendin-4 treatment in vivo and in vitro. Lineage tracing to label the glucagon-producing alpha-cells showed a higher proportion of regenerated beta-cells from alpha-cells in rAd-GLP-1-treated Glucagon-rtTA;Tet-O-Cre;R26-YFP mice than rAd producing beta-galactosidase-treated mice. In addition, exendin-4 increased the expression and secretion of fibroblast growth factor 21 (FGF21) in alphaTC1-9 cells and beta-cell-ablated islets. FGF21 treatment of beta-cell-ablated islets increased the expression of pancreatic and duodenal homeobox-1 and neurogenin-3 and significantly increased insulin(+)glucagon(+) cells. Generation of insulin(+)glucagon(+) cells by exendin-4 was significantly reduced in islets transfected with FGF21 small interfering RNA or islets of FGF21 knockout mice. Generation of insulin(+) cells by rAd-GLP-1 treatment was significantly reduced in FGF21 knockout mice compared with wild-type mice. We suggest that GLP-1 has an important role in alpha-cell transdifferentiation to generate new beta-cells, which might be mediated, in part, by FGF21 induction. |
