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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...

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Autores principales: Szendroedi, Julia, Frossard, Martin, Klein, Nikolas, Bieglmayer, Christian, Wagner, Oswald, Pacini, Giovanni, Decker, Janette, Nowotny, Peter, Müller, Markus, Roden, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
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.
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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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