Abstract
Under extreme conditions or by genetic modification, pancreatic α-cells can regenerate and be converted into β-cells. This regeneration holds substantial promise for cell replacement therapy in diabetic patients. The discovery of clinical therapeutic strategies to promote β-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 α-cell neogenesis, and promoted α-cell proliferation. Strikingly, the treatment also increased the β-cell mass in these two T1D models. Using α-cell lineage-tracing mice, we found that the neogenic β-cells were likely derived from α-cell conversion. Therefore, GCGR mAb-induced α- to β-cell conversion might represent a pre-clinical approach for improving diabetes therapy.