Antagonistic Glucagon Receptor Antibody Promotes ?-Cell Proliferation and Increases ?-Cell Mass in Diabetic Mice.

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

SUBMITTER: Wei R 

PROVIDER: S-EPMC6581654 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature