| Autor: |
Xi, Yannan, Song, Benbo, Ngan, Iris, Solloway, Mark J., Humphrey, Mark, Wang, Yan, Mondal, Kalyani, Wu, Hao, Liu, Wenhui, Lindhout, Darrin A., Li, Diana, Matern, Hugo, Kekatpure, Avantika, Haldankar, Raj, Kaplan, Daniel D., Yang, Hong, Pedersen, Ophelia, Chen, Anna, Zhou, Mei, Winans, Bethany, Guo, Wei, Kutach, Alan, Fanget, Marie, Fox, Michael, Tang, Jie, Zha, Jiping, Younis, Husam, Shen, David, DePaoli, Alex, Tian, Hui, Liu, Zhonghao |
| Zdroj: |
Cell Reports; May 2022, Vol. 39 Issue: 9 |
| Abstrakt: |
Type 1 diabetes mellitus (T1D) is a chronic disease with potentially severe complications, and β-cell deficiency underlies this disease. Despite active research, no therapy to date has been able to induce β-cell regeneration in humans. Here, we discover the β-cell regenerative effects of glucagon receptor antibody (anti-GcgR). Treatment with anti-GcgR in mouse models of β-cell deficiency leads to reversal of hyperglycemia, increase in plasma insulin levels, and restoration of β-cell mass. We demonstrate that both β-cell proliferation and α- to β-cell transdifferentiation contribute to anti-GcgR-induced β-cell regeneration. Interestingly, anti-GcgR-induced α-cell hyperplasia can be uncoupled from β-cell regeneration after antibody clearance from the body. Importantly, we are able to show that anti-GcgR-induced β-cell regeneration is also observed in non-human primates. Furthermore, anti-GcgR and anti-CD3 combination therapy reverses diabetes and increases β-cell mass in a mouse model of autoimmune diabetes. |
| Databáze: |
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