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

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....

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Autores principales: Zhang, Wei, Wu, Mengrui, Kim, Teayoun, Jariwala, Ravi H., Garvey, W. John, Luo, Nanlan, Kang, Minsung, Ma, Elizabeth, Tian, Ling, Steverson, Dennis, Yang, Qinglin, Fu, Yuchang, Garvey, W. Timothy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955990/
https://www.ncbi.nlm.nih.gov/pubmed/27207527
http://dx.doi.org/10.2337/db16-0154
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author Zhang, Wei
Wu, Mengrui
Kim, Teayoun
Jariwala, Ravi H.
Garvey, W. John
Luo, Nanlan
Kang, Minsung
Ma, Elizabeth
Tian, Ling
Steverson, Dennis
Yang, Qinglin
Fu, Yuchang
Garvey, W. Timothy
author_facet Zhang, Wei
Wu, Mengrui
Kim, Teayoun
Jariwala, Ravi H.
Garvey, W. John
Luo, Nanlan
Kang, Minsung
Ma, Elizabeth
Tian, Ling
Steverson, Dennis
Yang, Qinglin
Fu, Yuchang
Garvey, W. Timothy
author_sort Zhang, Wei
collection PubMed
description 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.
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spelling pubmed-49559902017-08-01 Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet–Induced Insulin Resistance Zhang, Wei Wu, Mengrui Kim, Teayoun Jariwala, Ravi H. Garvey, W. John Luo, Nanlan Kang, Minsung Ma, Elizabeth Tian, Ling Steverson, Dennis Yang, Qinglin Fu, Yuchang Garvey, W. Timothy Diabetes Pathophysiology 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. American Diabetes Association 2016-08 2016-05-10 /pmc/articles/PMC4955990/ /pubmed/27207527 http://dx.doi.org/10.2337/db16-0154 Text en © 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.
spellingShingle Pathophysiology
Zhang, Wei
Wu, Mengrui
Kim, Teayoun
Jariwala, Ravi H.
Garvey, W. John
Luo, Nanlan
Kang, Minsung
Ma, Elizabeth
Tian, Ling
Steverson, Dennis
Yang, Qinglin
Fu, Yuchang
Garvey, W. Timothy
Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet–Induced Insulin Resistance
title Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet–Induced Insulin Resistance
title_full Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet–Induced Insulin Resistance
title_fullStr Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet–Induced Insulin Resistance
title_full_unstemmed Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet–Induced Insulin Resistance
title_short Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet–Induced Insulin Resistance
title_sort skeletal muscle trib3 mediates glucose toxicity in diabetes and high- fat diet–induced insulin resistance
topic Pathophysiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955990/
https://www.ncbi.nlm.nih.gov/pubmed/27207527
http://dx.doi.org/10.2337/db16-0154
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