Glucagon-receptor-antagonism-mediated β-cell regeneration as an effective anti-diabetic therapy

Type 1 diabetes mellitus (T1D) is a chronic disease with potentially severe complications, and beta-cell deficiency underlies this disease. Despite active research, no therapy to date has been able to induce beta-cell regeneration in humans. Here, we discover the beta-cell regenerative effects of glucagon receptor antibody (anti-GcgR). Treatment with anti-GcgR in mouse models of beta-cell deficiency leads to reversal of hyperglycemia, increase in plasma insulin levels, and restoration of beta-cell mass. We demonstrate that both beta-cell proliferation and alpha- to beta-cell transdifferentiation contribute to anti-GcgR-induced beta-cell regeneration. Interestingly, anti-GcgR-induced cc-cell hyperplasia can be uncoupled from beta-cell regeneration after antibody clearance from the body. Importantly, we are able to show that anti-GcgR-induced beta-cell regeneration is also observed in non-human primates. Furthermore, anti-GcgR and anti-CD3 combination therapy reverses diabetes and increases beta-cell mass in a mouse model of autoimmune diabetes.

Automated summary

Anti-glucagon receptor antibody can induce beta-cell regeneration, reversing diabetes and restoring insulin levels. This therapy is effective in mouse models and non-human primates.