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Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism
Protein kinase C (PKC)δ has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKCδ in skeletal muscle in the control of insulin sensitivity and glucose met...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657586/ https://www.ncbi.nlm.nih.gov/pubmed/26307588 http://dx.doi.org/10.2337/db14-1891 |
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author | Li, Mengyao Vienberg, Sara G. Bezy, Olivier O’Neill, Brian T. Kahn, C. Ronald |
author_facet | Li, Mengyao Vienberg, Sara G. Bezy, Olivier O’Neill, Brian T. Kahn, C. Ronald |
author_sort | Li, Mengyao |
collection | PubMed |
description | Protein kinase C (PKC)δ has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKCδ in skeletal muscle in the control of insulin sensitivity and glucose metabolism by generating mice in which PKCδ was deleted specifically in muscle using Cre-lox recombination. Deletion of PKCδ in muscle improved insulin signaling in young mice, especially at low insulin doses; however, this did not change glucose tolerance or insulin tolerance tests done with pharmacological levels of insulin. Likewise, in young mice, muscle-specific deletion of PKCδ did not rescue high-fat diet–induced insulin resistance or glucose intolerance. However, with an increase in age, PKCδ levels in muscle increased, and by 6 to 7 months of age, muscle-specific deletion of PKCδ improved whole-body insulin sensitivity and muscle insulin resistance and by 15 months of age improved the age-related decline in whole-body glucose tolerance. At 15 months of age, M-PKCδKO mice also exhibited decreased metabolic rate and lower levels of some proteins of the OXPHOS complex suggesting a role for PKCδ in the regulation of mitochondrial mass at older age. These data indicate an important role of PKCδ in the regulation of insulin sensitivity and mitochondrial homeostasis in skeletal muscle with aging. |
format | Online Article Text |
id | pubmed-4657586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-46575862016-12-01 Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism Li, Mengyao Vienberg, Sara G. Bezy, Olivier O’Neill, Brian T. Kahn, C. Ronald Diabetes Metabolism Protein kinase C (PKC)δ has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKCδ in skeletal muscle in the control of insulin sensitivity and glucose metabolism by generating mice in which PKCδ was deleted specifically in muscle using Cre-lox recombination. Deletion of PKCδ in muscle improved insulin signaling in young mice, especially at low insulin doses; however, this did not change glucose tolerance or insulin tolerance tests done with pharmacological levels of insulin. Likewise, in young mice, muscle-specific deletion of PKCδ did not rescue high-fat diet–induced insulin resistance or glucose intolerance. However, with an increase in age, PKCδ levels in muscle increased, and by 6 to 7 months of age, muscle-specific deletion of PKCδ improved whole-body insulin sensitivity and muscle insulin resistance and by 15 months of age improved the age-related decline in whole-body glucose tolerance. At 15 months of age, M-PKCδKO mice also exhibited decreased metabolic rate and lower levels of some proteins of the OXPHOS complex suggesting a role for PKCδ in the regulation of mitochondrial mass at older age. These data indicate an important role of PKCδ in the regulation of insulin sensitivity and mitochondrial homeostasis in skeletal muscle with aging. American Diabetes Association 2015-12 2015-08-25 /pmc/articles/PMC4657586/ /pubmed/26307588 http://dx.doi.org/10.2337/db14-1891 Text en © 2015 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 | Metabolism Li, Mengyao Vienberg, Sara G. Bezy, Olivier O’Neill, Brian T. Kahn, C. Ronald Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism |
title | Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism |
title_full | Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism |
title_fullStr | Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism |
title_full_unstemmed | Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism |
title_short | Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism |
title_sort | role of pkcδ in insulin sensitivity and skeletal muscle metabolism |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657586/ https://www.ncbi.nlm.nih.gov/pubmed/26307588 http://dx.doi.org/10.2337/db14-1891 |
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