| First Author | Damond N | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27092792 | Mgi Jnum | J:269719 |
| Mgi Id | MGI:6206104 | Doi | 10.7554/eLife.13828 |
| Citation | Damond N, et al. (2016) Blockade of glucagon signaling prevents or reverses diabetes onset only if residual beta-cells persist. Elife 5:e13828 |
| abstractText | Glucagon secretion dysregulation in diabetes fosters hyperglycemia. Recent studies report that mice lacking glucagon receptor (Gcgr(-/-)) do not develop diabetes following streptozotocin (STZ)-mediated ablation of insulin-producing beta-cells. Here, we show that diabetes prevention in STZ-treated Gcgr(-/-) animals requires remnant insulin action originating from spared residual beta-cells: these mice indeed became hyperglycemic after insulin receptor blockade. Accordingly, Gcgr(-/-) mice developed hyperglycemia after induction of a more complete, diphtheria toxin (DT)-induced beta-cell loss, a situation of near-absolute insulin deficiency similar to type 1 diabetes. In addition, glucagon deficiency did not impair the natural capacity of alpha-cells to reprogram into insulin production after extreme beta-cell loss. alpha-to-beta-cell conversion was improved in Gcgr(-/-) mice as a consequence of alpha-cell hyperplasia. Collectively, these results indicate that glucagon antagonism could i) be a useful adjuvant therapy in diabetes only when residual insulin action persists, and ii) help devising future beta-cell regeneration therapies relying upon alpha-cell reprogramming. |
