| First Author | Cui X | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 7 | Pages | 104567 |
| PubMed ID | 35789836 | Mgi Jnum | J:349854 |
| Mgi Id | MGI:7313932 | Doi | 10.1016/j.isci.2022.104567 |
| Citation | Cui X, et al. (2022) Pro-alpha-cell-derived beta-cells contribute to beta-cell neogenesis induced by antagonistic glucagon receptor antibody in type 2 diabetic mice. iScience 25(7):104567 |
| abstractText | The deficiency of pancreatic beta-cells is the key pathogenesis of diabetes, while glucagon-secreting alpha-cells are another player in the development of diabetes. Here, we aimed to investigate the effects of glucagon receptor (GCGR) antagonism on beta-cell neogenesis in type 2 diabetic (T2D) mice and explore the origins of the neogenic beta-cells. We showed that GCGR monoclonal antibody (mAb) elevated plasma insulin level and increased beta-cell mass in T2D mice. By using alpha-cell lineage-tracing (glucagon -cre -beta-gal) mice and inducible Ngn3(+) pancreatic endocrine progenitor lineage-tracing (Ngn3-CreERT2-tdTomato) mice, we found that GCGR mAb treatment promoted alpha-cell regression to progenitors, and induced Ngn3(+) progenitor reactivation and differentiation toward beta-cells. Besides, GCGR mAb upregulated the expression levels of beta-cell regeneration-associated genes and promoted insulin secretion in primary mouse islets, indicative of a direct effect on beta-cell identity. Our findings suggest that GCGR antagonism not only increases insulin secretion but also promotes pro-alpha-cell-derived beta-cell neogenesis in T2D mice. |
