DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells

DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in... Abstract The increased availability of saturated lipids has been correlated with development of insulin resistance, although the basis for this impairment is not defined. This work examined the interaction of saturated and unsaturated fatty acids (FA) with insulin stimulation of glucose uptake and its relation to the FA incorporation into different lipid pools in cultured human muscle. It is shown that basal or insulin-stimulated 2-deoxyglucose uptake was unaltered in cells preincubated with oleate, whereas basal glucose uptake was increased and insulin response was impaired in palmitate- and stearate-loaded cells. Analysis of the incorporation of FA into different lipid pools showed that palmitate, stearate, and oleate were similarly incorporated into phospholipids (PL) and did not modify the FA profile. In contrast, differences were observed in the total incorporation of FA into triacylglycerides (TAG): unsaturated FA were readily diverted toward TAG, whereas saturated FA could accumulate as diacylglycerol (DAG). Treatment with palmitate increased the activity of membrane-associated protein kinase C, whereas oleate had no effect. Mixture of palmitate with oleate diverted the saturated FA toward TAG and abolished its effect on glucose uptake. In conclusion, our data indicate that saturated FA-promoted changes in basal glucose uptake and insulin response were not correlated to a modification of the FA profile in PL or TAG accumulation. In contrast, these changes were related to saturated FA being accumulated as DAG and activating protein kinase C. Therefore, our results suggest that accumulation of DAG may be a molecular link between an increased availability of saturated FA and the induction of insulin resistance. insulin sensitivity skeletal muscle glucose uptake diacylglycerol triacylglyceride saturated fatty acids Footnotes E. Montell was the recipient of a fellowship Formación Personal Investigador from the Ministerio de Educación y Cultura (Spain). Address for reprint requests and other correspondence: A. M. Gómez-Foix, Departament de Bioquı́mica i Biologia Molecular, Universitat de Barcelona, Martı́ i Franqués 1, 08028-Barcelona, Spain (E-mail: anamaria@sun.bq.ub.es ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 2001 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Endocrinology and Metabolism The American Physiological Society

DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1849
eISSN
1522-1555
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Abstract

Abstract The increased availability of saturated lipids has been correlated with development of insulin resistance, although the basis for this impairment is not defined. This work examined the interaction of saturated and unsaturated fatty acids (FA) with insulin stimulation of glucose uptake and its relation to the FA incorporation into different lipid pools in cultured human muscle. It is shown that basal or insulin-stimulated 2-deoxyglucose uptake was unaltered in cells preincubated with oleate, whereas basal glucose uptake was increased and insulin response was impaired in palmitate- and stearate-loaded cells. Analysis of the incorporation of FA into different lipid pools showed that palmitate, stearate, and oleate were similarly incorporated into phospholipids (PL) and did not modify the FA profile. In contrast, differences were observed in the total incorporation of FA into triacylglycerides (TAG): unsaturated FA were readily diverted toward TAG, whereas saturated FA could accumulate as diacylglycerol (DAG). Treatment with palmitate increased the activity of membrane-associated protein kinase C, whereas oleate had no effect. Mixture of palmitate with oleate diverted the saturated FA toward TAG and abolished its effect on glucose uptake. In conclusion, our data indicate that saturated FA-promoted changes in basal glucose uptake and insulin response were not correlated to a modification of the FA profile in PL or TAG accumulation. In contrast, these changes were related to saturated FA being accumulated as DAG and activating protein kinase C. Therefore, our results suggest that accumulation of DAG may be a molecular link between an increased availability of saturated FA and the induction of insulin resistance. insulin sensitivity skeletal muscle glucose uptake diacylglycerol triacylglyceride saturated fatty acids Footnotes E. Montell was the recipient of a fellowship Formación Personal Investigador from the Ministerio de Educación y Cultura (Spain). Address for reprint requests and other correspondence: A. M. Gómez-Foix, Departament de Bioquı́mica i Biologia Molecular, Universitat de Barcelona, Martı́ i Franqués 1, 08028-Barcelona, Spain (E-mail: anamaria@sun.bq.ub.es ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 2001 the American Physiological Society

Journal

AJP - Endocrinology and MetabolismThe American Physiological Society

Published: Feb 1, 2001

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