| First Author | Zhao H | Year | 2017 |
| Journal | Diabetes | Volume | 66 |
| Issue | 7 | Pages | 1833-1846 |
| PubMed ID | 28461456 | Mgi Jnum | J:246712 |
| Mgi Id | MGI:5923409 | Doi | 10.2337/db16-1277 |
| Citation | Zhao H, et al. (2017) Elovl6 Deficiency Improves Glycemic Control in Diabetic db/db Mice by Expanding beta-Cell Mass and Increasing Insulin Secretory Capacity. Diabetes 66(7):1833-1846 |
| abstractText | Dysfunctional fatty acid (FA) metabolism plays an important role in the pathogenesis of beta-cell dysfunction and loss of beta-cell mass in type 2 diabetes (T2D). Elovl6 is a microsomal enzyme that is responsible for converting C16 saturated and monounsaturated FAs into C18 species. We previously showed that Elovl6 played a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further define its role in T2D development, we assessed the effects of Elovl6 deletion in leptin receptor-deficient C57BL/KsJ db/db mice, a model of T2D. The db/db;Elovl6-/- mice had a markedly increased beta-cell mass with increased proliferation and decreased apoptosis, an adaptive increase in insulin, and improved glycemic control. db/db islets were characterized by a prominent elevation of oleate (C18:1n-9), cell stress, and inflammation, which was completely suppressed by Elovl6 deletion. As a mechanistic ex vivo experiment, isolated islets from Elovl6-/- mice exhibited reduced susceptibility to palmitate-induced inflammation, endoplasmic reticulum stress, and beta-cell apoptosis. In contrast, oleate-treated islets resulted in impaired glucose-stimulated insulin secretion with suppressed related genes irrespective of the Elovl6 gene. Taken together, Elovl6 is a fundamental factor linking dysregulated lipid metabolism to beta-cell dysfunction, islet inflammation, and beta-cell apoptosis in T2D, highlighting oleate as the potential culprit of beta-cell lipotoxicity. |
