Elovl6 Deficiency Improves Glycemic Control in Diabetic db/db Mice by Expanding ß-Cell Mass and Increasing Insulin Secretory Capacity.
Diabetes
; 66(7): 1833-1846, 2017 07.
Article
en En
| MEDLINE
| ID: mdl-28461456
ABSTRACT
Dysfunctional fatty acid (FA) metabolism plays an important role in the pathogenesis of ß-cell dysfunction and loss of ß-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 ß-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 (C181n-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 ß-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 ß-cell dysfunction, islet inflammation, and ß-cell apoptosis in T2D, highlighting oleate as the potential culprit of ß-cell lipotoxicity.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Acetiltransferasas
/
Diabetes Mellitus Experimental
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Diabetes Mellitus Tipo 2
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Células Secretoras de Insulina
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Insulina
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Diabetes
Año:
2017
Tipo del documento:
Article