| First Author | Xi Y | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 9 | Pages | 110872 |
| PubMed ID | 35649369 | Mgi Jnum | J:326148 |
| Mgi Id | MGI:7294028 | Doi | 10.1016/j.celrep.2022.110872 |
| Citation | Xi Y, et al. (2022) Glucagon-receptor-antagonism-mediated beta-cell regeneration as an effective anti-diabetic therapy. Cell Rep 39(9):110872 |
| abstractText | 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 alpha-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. |
