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

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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

Title: Palmitate and oleate exert differential effects on insulin signalling and glucose uptake in human skeletal muscle cells
Author: Makinen, Selina; Nguyen, Yen H.; Skrobuk, Paulina; Koistinen, Heikki A.
Contributor organization: Clinicum
Department of Medicine
Endokrinologian yksikkö
University of Helsinki
HUS Internal Medicine and Rehabilitation
HUS Abdominal Center
Date: 2017-07-01
Language: eng
Number of pages: 9
Belongs to series: Endocrine Connections
ISSN: 2049-3614
DOI: https://doi.org/10.1530/EC-17-0039
URI: http://hdl.handle.net/10138/225803
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.
Subject: ER stress
fatty acid
glucose uptake
human
insulin signalling
skeletal muscle
FATTY-ACID OXIDATION
RESISTANCE
STRESS
INFLAMMATION
SENSITIVITY
OBESITY
DIET
CARBOHYDRATE
ACCUMULATION
PREVENTION
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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