Palmitate and oleate exert differential effects on insulin signalling and glucose uptake in human skeletal muscle cells

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dc.contributor.author Makinen, Selina
dc.contributor.author Nguyen, Yen H.
dc.contributor.author Skrobuk, Paulina
dc.contributor.author Koistinen, Heikki A.
dc.date.accessioned 2017-10-13T10:46:05Z
dc.date.available 2017-10-13T10:46:05Z
dc.date.issued 2017-07-01
dc.identifier.citation Makinen , S , Nguyen , Y H , Skrobuk , P & Koistinen , H A 2017 , ' Palmitate and oleate exert differential effects on insulin signalling and glucose uptake in human skeletal muscle cells ' , Endocrine Connections , vol. 6 , no. 5 , pp. 331-339 . https://doi.org/10.1530/EC-17-0039
dc.identifier.other PURE: 90984646
dc.identifier.other PURE UUID: 641cf7c4-9345-4de0-9b1a-e15ca2b20162
dc.identifier.other WOS: 000411645500004
dc.identifier.other Scopus: 85026203873
dc.identifier.other ORCID: /0000-0001-7870-070X/work/104829464
dc.identifier.uri http://hdl.handle.net/10138/225803
dc.description.abstract Saturated fatty acids are implicated in the development of insulin resistance, whereas unsaturated fatty acids may have a protective effect on metabolism. We tested in primary human myotubes if insulin resistance induced by saturated fatty acid palmitate can be ameliorated by concomitant exposure to unsaturated fatty acid oleate. Primary human myotubes were pretreated with palmitate, oleate or their combination for 12 h. Glucose uptake was determined by intracellular accumulation of [H-3]-2-deoxy-d-glucose, insulin signalling and activation of endoplasmic reticulum (ER) stress by Western blotting, and mitochondrial reactive oxygen species (ROS) production by fluorescent dye MitoSOX. Exposure of primary human myotubes to palmitate impaired insulin-stimulated Akt-Ser(473), AS160 and GSK-3 beta phosphorylation, induced ER stress signalling target PERK and stress kinase JNK 54 kDa isoform. These effects were virtually abolished by concomitant exposure of palmitate-treated myotubes to oleate. However, an exposure to palmitate, oleate or their combination reduced insulin-stimulated glucose uptake. This was associated with increased mitochondrial ROS production in palmitate-treated myotubes co-incubated with oleate, and was alleviated by antioxidants MitoTempo and Tempol. Thus, metabolic and intracellular signalling events diverge in myotubes treated with palmitate and oleate. Exposure of human myotubes to excess fatty acids increases ROS production and induces insulin resistance. en
dc.format.extent 9
dc.language.iso eng
dc.relation.ispartof Endocrine Connections
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject ER stress
dc.subject fatty acid
dc.subject glucose uptake
dc.subject human
dc.subject insulin signalling
dc.subject skeletal muscle
dc.subject FATTY-ACID OXIDATION
dc.subject RESISTANCE
dc.subject STRESS
dc.subject INFLAMMATION
dc.subject SENSITIVITY
dc.subject OBESITY
dc.subject DIET
dc.subject CARBOHYDRATE
dc.subject ACCUMULATION
dc.subject PREVENTION
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title Palmitate and oleate exert differential effects on insulin signalling and glucose uptake in human skeletal muscle cells en
dc.type Article
dc.contributor.organization Clinicum
dc.contributor.organization Department of Medicine
dc.contributor.organization Endokrinologian yksikkö
dc.contributor.organization University of Helsinki
dc.contributor.organization HUS Internal Medicine and Rehabilitation
dc.contributor.organization HUS Abdominal Center
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1530/EC-17-0039
dc.relation.issn 2049-3614
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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