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Nutrients 2016, 8(3), 164; doi:10.3390/nu8030164

Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

1
Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht 6200 MD, The Netherlands
2
Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam 1007 MB, The Netherlands
Deceased on Date.
*
Author to whom correspondence should be addressed.
Received: 12 January 2016 / Revised: 24 February 2016 / Accepted: 9 March 2016 / Published: 14 March 2016
(This article belongs to the Special Issue Fatty Acids in Obesity and Type 2 Diabetes)
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Abstract

Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-13C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects. View Full-Text
Keywords: skeletal muscle; lipid metabolism; insulin resistance; impaired glucose tolerance; impaired fasting glucose skeletal muscle; lipid metabolism; insulin resistance; impaired glucose tolerance; impaired fasting glucose
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Goossens, G.H.; Moors, C.C.M.; Jocken, J.W.E.; van der Zijl, N.J.; Jans, A.; Konings, E.; Diamant, M.; Blaak, E.E. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose. Nutrients 2016, 8, 164.

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