Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet-Induced Insulin Resistance.

Autor:	Zhang W; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL garveyt@uab.edu siweizh@uab.edu., Wu M; Department of Molecular & Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL., Kim T; Department of Medicine-Endocrinology, Diabetes & Metabolism, University of Alabama at Birmingham, Birmingham, AL., Jariwala RH; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL., Garvey WJ; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL., Luo N; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL., Kang M; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL., Ma E; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL., Tian L; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL., Steverson D; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL., Yang Q; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL., Fu Y; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL., Garvey WT; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL Birmingham Veterans Affairs Medical Center, Birmingham, AL garveyt@uab.edu siweizh@uab.edu.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2016 Aug; Vol. 65 (8), pp. 2380-91. Date of Electronic Publication: 2016 May 10.
DOI:	10.2337/db16-0154
Abstrakt:	In the current study, we used muscle-specific TRIB3 overexpressing (MOE) and knockout (MKO) mice to determine whether TRIB3 mediates glucose-induced insulin resistance in diabetes and whether alterations in TRIB3 expression as a function of nutrient availability have a regulatory role in metabolism. In streptozotocin diabetic mice, TRIB3 MOE exacerbated, whereas MKO prevented, glucose-induced insulin resistance and impaired glucose oxidation and defects in insulin signal transduction compared with wild-type (WT) mice, indicating that glucose-induced insulin resistance was dependent on TRIB3. In response to a high-fat diet, TRIB3 MOE mice exhibited greater weight gain and worse insulin resistance in vivo compared with WT mice, coupled with decreased AKT phosphorylation, increased inflammation and oxidative stress, and upregulation of lipid metabolic genes coupled with downregulation of glucose metabolic genes in skeletal muscle. These effects were prevented in the TRIB3 MKO mice relative to WT mice. In conclusion, TRIB3 has a pathophysiological role in diabetes and a physiological role in metabolism. Glucose-induced insulin resistance and insulin resistance due to diet-induced obesity both depend on muscle TRIB3. Under physiological conditions, muscle TRIB3 also influences energy expenditure and substrate metabolism, indicating that the decrease and increase in muscle TRIB3 under fasting and nutrient excess, respectively, are critical for metabolic homeostasis. (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
Databáze:	MEDLINE
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