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Lipid-Induced Insulin Resistance Is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans
Increased lipid availability reduces insulin-stimulated glucose disposal in skeletal muscle, which is generally explained by fatty acid–mediated inhibition of insulin signaling. It remains unclear whether lipids also impair transcapillary transport of insulin and glucose, which could become rate con...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501866/ https://www.ncbi.nlm.nih.gov/pubmed/22891212 http://dx.doi.org/10.2337/db12-0108 |
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author | Szendroedi, Julia Frossard, Martin Klein, Nikolas Bieglmayer, Christian Wagner, Oswald Pacini, Giovanni Decker, Janette Nowotny, Peter Müller, Markus Roden, Michael |
author_facet | Szendroedi, Julia Frossard, Martin Klein, Nikolas Bieglmayer, Christian Wagner, Oswald Pacini, Giovanni Decker, Janette Nowotny, Peter Müller, Markus Roden, Michael |
author_sort | Szendroedi, Julia |
collection | PubMed |
description | Increased lipid availability reduces insulin-stimulated glucose disposal in skeletal muscle, which is generally explained by fatty acid–mediated inhibition of insulin signaling. It remains unclear whether lipids also impair transcapillary transport of insulin and glucose, which could become rate controlling for glucose disposal. We hypothesized that lipid-induced insulin resistance is induced by inhibiting myocellular glucose uptake and not by interfering with the delivery of insulin or glucose. We measured changes in interstitial glucose and insulin in skeletal muscle of healthy volunteers during intravenous administration of triglycerides plus heparin or glycerol during physiologic and supraphysiologic hyperinsulinemia, by combining microdialysis with oral glucose tolerance tests and euglycemic-hyperinsulinemic clamps. Lipid infusion reduced insulin-stimulated glucose disposal by ∼70% (P < 0.05) during clamps and dynamic insulin sensitivity by ∼12% (P < 0.05) during oral glucose loading. Dialysate insulin and glucose levels were unchanged or even transiently higher (P < 0.05) during lipid than during glycerol infusion, whereas regional blood flow remained unchanged. These results demonstrate that short-term elevation of free fatty acids (FFAs) induces insulin resistance, which in skeletal muscle occurs primarily at the cellular level, without impairment of local perfusion or transcapillary transport of insulin and glucose. Thus, vascular effects of FFAs are not rate controlling for muscle insulin-stimulated glucose disposal. |
format | Online Article Text |
id | pubmed-3501866 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-35018662013-12-01 Lipid-Induced Insulin Resistance Is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans Szendroedi, Julia Frossard, Martin Klein, Nikolas Bieglmayer, Christian Wagner, Oswald Pacini, Giovanni Decker, Janette Nowotny, Peter Müller, Markus Roden, Michael Diabetes Metabolism Increased lipid availability reduces insulin-stimulated glucose disposal in skeletal muscle, which is generally explained by fatty acid–mediated inhibition of insulin signaling. It remains unclear whether lipids also impair transcapillary transport of insulin and glucose, which could become rate controlling for glucose disposal. We hypothesized that lipid-induced insulin resistance is induced by inhibiting myocellular glucose uptake and not by interfering with the delivery of insulin or glucose. We measured changes in interstitial glucose and insulin in skeletal muscle of healthy volunteers during intravenous administration of triglycerides plus heparin or glycerol during physiologic and supraphysiologic hyperinsulinemia, by combining microdialysis with oral glucose tolerance tests and euglycemic-hyperinsulinemic clamps. Lipid infusion reduced insulin-stimulated glucose disposal by ∼70% (P < 0.05) during clamps and dynamic insulin sensitivity by ∼12% (P < 0.05) during oral glucose loading. Dialysate insulin and glucose levels were unchanged or even transiently higher (P < 0.05) during lipid than during glycerol infusion, whereas regional blood flow remained unchanged. These results demonstrate that short-term elevation of free fatty acids (FFAs) induces insulin resistance, which in skeletal muscle occurs primarily at the cellular level, without impairment of local perfusion or transcapillary transport of insulin and glucose. Thus, vascular effects of FFAs are not rate controlling for muscle insulin-stimulated glucose disposal. American Diabetes Association 2012-12 2012-11-15 /pmc/articles/PMC3501866/ /pubmed/22891212 http://dx.doi.org/10.2337/db12-0108 Text en © 2012 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. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Metabolism Szendroedi, Julia Frossard, Martin Klein, Nikolas Bieglmayer, Christian Wagner, Oswald Pacini, Giovanni Decker, Janette Nowotny, Peter Müller, Markus Roden, Michael Lipid-Induced Insulin Resistance Is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans |
title | Lipid-Induced Insulin Resistance Is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans |
title_full | Lipid-Induced Insulin Resistance Is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans |
title_fullStr | Lipid-Induced Insulin Resistance Is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans |
title_full_unstemmed | Lipid-Induced Insulin Resistance Is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans |
title_short | Lipid-Induced Insulin Resistance Is Not Mediated by Impaired Transcapillary Transport of Insulin and Glucose in Humans |
title_sort | lipid-induced insulin resistance is not mediated by impaired transcapillary transport of insulin and glucose in humans |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501866/ https://www.ncbi.nlm.nih.gov/pubmed/22891212 http://dx.doi.org/10.2337/db12-0108 |
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