| First Author | Tang W | Year | 2017 |
| Journal | Mol Cell Endocrinol | Volume | 439 |
| Pages | 297-307 | PubMed ID | 27658750 |
| Mgi Jnum | J:252828 | Mgi Id | MGI:6095352 |
| Doi | 10.1016/j.mce.2016.09.015 | Citation | Tang W, et al. (2017) Exenatide substantially improves proinsulin conversion and cell survival that augment Ins2(+/Akita) beta cell function. Mol Cell Endocrinol 439:297-307 |
| abstractText | Proinsulin folding imperfections cause extensive beta-cell defects known in diabetes. Here, we investigated whether exenatide can alleviate such defects in proinsulin conversion, beta-cell survival, and insulin secretion, in the Ins2(+/Akita) beta-cells that have a spontaneous mutation (Cys 96 Tyr) in the insulin 2 gene caused dominant negative misfolding problem. 15 or 120 min exenatide administration substantially improves glucose-stimulated insulin secretion, marked in the secreted insulin levels and proinsulin/insulin ratio. This improvement is mainly due to enhanced conversion of proinsulin to insulin, having nothing to do with the prohormone convertase PC1/3 and PC2 levels. The 15 min improvement is calcium-independent. The 120 min improvement is linked to calcium and/or cAMP dependent mechanisms. This efficacy is validated during longer treatment and in Akita islets. Exenatide improves Ins2(+/Akita) beta-cell survival and Akita mouse's glucose tolerance. The results suggest a potential of incretin mimetics in alleviating defective proinsulin conversion and other proinsulin misfolding consequences. |
