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Insulin Increases Ceramide Synthesis in Skeletal Muscle

Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle. Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG) were isolated and gene expression of multiple bios...

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Autores principales: Hansen, M. E., Tippetts, T. S., Anderson, M. C., Holub, Z. E., Moulton, E. R., Swensen, A. C., Prince, J. T., Bikman, B. T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052187/
https://www.ncbi.nlm.nih.gov/pubmed/24949486
http://dx.doi.org/10.1155/2014/765784
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author Hansen, M. E.
Tippetts, T. S.
Anderson, M. C.
Holub, Z. E.
Moulton, E. R.
Swensen, A. C.
Prince, J. T.
Bikman, B. T.
author_facet Hansen, M. E.
Tippetts, T. S.
Anderson, M. C.
Holub, Z. E.
Moulton, E. R.
Swensen, A. C.
Prince, J. T.
Bikman, B. T.
author_sort Hansen, M. E.
collection PubMed
description Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle. Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG) were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis. Results. In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals. Conclusions. This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects.
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spelling pubmed-40521872014-06-19 Insulin Increases Ceramide Synthesis in Skeletal Muscle Hansen, M. E. Tippetts, T. S. Anderson, M. C. Holub, Z. E. Moulton, E. R. Swensen, A. C. Prince, J. T. Bikman, B. T. J Diabetes Res Research Article Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle. Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG) were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis. Results. In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals. Conclusions. This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects. Hindawi Publishing Corporation 2014 2014-05-18 /pmc/articles/PMC4052187/ /pubmed/24949486 http://dx.doi.org/10.1155/2014/765784 Text en Copyright © 2014 M. E. Hansen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hansen, M. E.
Tippetts, T. S.
Anderson, M. C.
Holub, Z. E.
Moulton, E. R.
Swensen, A. C.
Prince, J. T.
Bikman, B. T.
Insulin Increases Ceramide Synthesis in Skeletal Muscle
title Insulin Increases Ceramide Synthesis in Skeletal Muscle
title_full Insulin Increases Ceramide Synthesis in Skeletal Muscle
title_fullStr Insulin Increases Ceramide Synthesis in Skeletal Muscle
title_full_unstemmed Insulin Increases Ceramide Synthesis in Skeletal Muscle
title_short Insulin Increases Ceramide Synthesis in Skeletal Muscle
title_sort insulin increases ceramide synthesis in skeletal muscle
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052187/
https://www.ncbi.nlm.nih.gov/pubmed/24949486
http://dx.doi.org/10.1155/2014/765784
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