| First Author | Wei R | Year | 2019 |
| Journal | iScience | Volume | 16 |
| Pages | 326-339 | PubMed ID | 31203188 |
| Mgi Jnum | J:352728 | Mgi Id | MGI:7706170 |
| Doi | 10.1016/j.isci.2019.05.030 | Citation | Wei R, et al. (2019) Antagonistic Glucagon Receptor Antibody Promotes alpha-Cell Proliferation and Increases beta-Cell Mass in Diabetic Mice. iScience 16:326-339 |
| abstractText | Under extreme conditions or by genetic modification, pancreatic alpha-cells can regenerate and be converted into beta-cells. This regeneration holds substantial promise for cell replacement therapy in diabetic patients. The discovery of clinical therapeutic strategies to promote beta-cell regeneration is crucial for translating these findings into clinical applications. In this study, we reported that treatment with REMD 2.59, a human glucagon receptor (GCGR) monoclonal antibody (mAb), lowered blood glucose without inducing hypoglycemia in normoglycemic, streptozotocin-induced type 1 diabetic (T1D) and non-obesity diabetic mice. Moreover, GCGR mAb treatment increased the plasma glucagon and active glucagon-like peptide-1 levels, induced pancreatic ductal ontogenic alpha-cell neogenesis, and promoted alpha-cell proliferation. Strikingly, the treatment also increased the beta-cell mass in these two T1D models. Using alpha-cell lineage-tracing mice, we found that the neogenic beta-cells were likely derived from alpha-cell conversion. Therefore, GCGR mAb-induced alpha- to beta-cell conversion might represent a pre-clinical approach for improving diabetes therapy. |
