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Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice
OBJECTIVE—We determined whether muscle AMP-activated protein kinase (AMPK) has a role in the development of insulin resistance. RESEARCH DESIGN AND METHODS—Muscle-specific transgenic mice expressing an inactive form of the AMPK α2 catalytic subunit (α2i TG) and their wild-type littermates were fed e...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570392/ https://www.ncbi.nlm.nih.gov/pubmed/18728234 http://dx.doi.org/10.2337/db07-1187 |
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author | Fujii, Nobuharu Ho, Richard C. Manabe, Yasuko Jessen, Niels Toyoda, Taro Holland, William L. Summers, Scott A. Hirshman, Michael F. Goodyear, Laurie J. |
author_facet | Fujii, Nobuharu Ho, Richard C. Manabe, Yasuko Jessen, Niels Toyoda, Taro Holland, William L. Summers, Scott A. Hirshman, Michael F. Goodyear, Laurie J. |
author_sort | Fujii, Nobuharu |
collection | PubMed |
description | OBJECTIVE—We determined whether muscle AMP-activated protein kinase (AMPK) has a role in the development of insulin resistance. RESEARCH DESIGN AND METHODS—Muscle-specific transgenic mice expressing an inactive form of the AMPK α2 catalytic subunit (α2i TG) and their wild-type littermates were fed either a high-fat (60% kcal fat) or a control (10% kcal fat) diet for 30 weeks. RESULTS—Compared with wild-type mice, glucose tolerance in α2i TG mice was slightly impaired on the control diet and significantly impaired on the high-fat diet. To determine whether the whole-body glucose intolerance was associated with impaired insulin sensitivity in skeletal muscle, glucose transport in response to submaximal insulin (450 μU/ml) was measured in isolated soleus muscles. On the control diet, insulin-stimulated glucose transport was reduced by ∼50% in α2i TG mice compared with wild-type mice. High-fat feeding partially decreased insulin-stimulated glucose transport in wild-type mice, while high-fat feeding resulted in a full blunting of insulin-stimulated glucose transport in the α2i TG mice. High-fat feeding in α2i TG mice was accompanied by decreased expression of insulin signaling proteins in gastrocnemius muscle. CONCLUSIONS—The lack of skeletal muscle AMPK α2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK α2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments. |
format | Text |
id | pubmed-2570392 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-25703922009-11-01 Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice Fujii, Nobuharu Ho, Richard C. Manabe, Yasuko Jessen, Niels Toyoda, Taro Holland, William L. Summers, Scott A. Hirshman, Michael F. Goodyear, Laurie J. Diabetes Metabolism OBJECTIVE—We determined whether muscle AMP-activated protein kinase (AMPK) has a role in the development of insulin resistance. RESEARCH DESIGN AND METHODS—Muscle-specific transgenic mice expressing an inactive form of the AMPK α2 catalytic subunit (α2i TG) and their wild-type littermates were fed either a high-fat (60% kcal fat) or a control (10% kcal fat) diet for 30 weeks. RESULTS—Compared with wild-type mice, glucose tolerance in α2i TG mice was slightly impaired on the control diet and significantly impaired on the high-fat diet. To determine whether the whole-body glucose intolerance was associated with impaired insulin sensitivity in skeletal muscle, glucose transport in response to submaximal insulin (450 μU/ml) was measured in isolated soleus muscles. On the control diet, insulin-stimulated glucose transport was reduced by ∼50% in α2i TG mice compared with wild-type mice. High-fat feeding partially decreased insulin-stimulated glucose transport in wild-type mice, while high-fat feeding resulted in a full blunting of insulin-stimulated glucose transport in the α2i TG mice. High-fat feeding in α2i TG mice was accompanied by decreased expression of insulin signaling proteins in gastrocnemius muscle. CONCLUSIONS—The lack of skeletal muscle AMPK α2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK α2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments. American Diabetes Association 2008-11 /pmc/articles/PMC2570392/ /pubmed/18728234 http://dx.doi.org/10.2337/db07-1187 Text en Copyright © 2008, 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. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Metabolism Fujii, Nobuharu Ho, Richard C. Manabe, Yasuko Jessen, Niels Toyoda, Taro Holland, William L. Summers, Scott A. Hirshman, Michael F. Goodyear, Laurie J. Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice |
title | Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice |
title_full | Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice |
title_fullStr | Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice |
title_full_unstemmed | Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice |
title_short | Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice |
title_sort | ablation of amp-activated protein kinase α2 activity exacerbates insulin resistance induced by high-fat feeding of mice |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570392/ https://www.ncbi.nlm.nih.gov/pubmed/18728234 http://dx.doi.org/10.2337/db07-1187 |
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