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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....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2016
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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. |
format | Online Article Text |
id | pubmed-4955990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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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