ANT1-mediated fatty acid-induced uncoupling as a target for improving myocellular insulin sensitivity

Diabetologia
Lauren M SparksJoris Hoeks

Abstract

Dissipating energy via mitochondrial uncoupling has been suggested to contribute to enhanced insulin sensitivity. We hypothesised that skeletal muscle mitochondria of endurance-trained athletes have increased sensitivity for fatty acid (FA)-induced uncoupling, which is driven by the mitochondrial protein adenine nucleotide translocase 1 (ANT1). Capacity for FA-induced uncoupling was measured in endurance-trained male athletes (T) and sedentary young men (UT) in an observational study and also in isolated skeletal muscle mitochondria from Zucker diabetic fatty (ZDF) rats and C2C12 myotubes following small interfering RNA (siRNA)-mediated gene silencing of ANT1. Thus, fuelled by glutamate/succinate (fibres) or pyruvate (mitochondria and myotubes) and in the presence of oligomycin to block ATP synthesis, increasing levels of oleate (fibres) or palmitate (mitochondria and myotubes) were automatically titrated while respiration was monitored. Insulin sensitivity was measured by hyperinsulinaemic-euglycaemic clamp in humans and via insulin-stimulated glucose uptake in myotubes. Skeletal muscle from the T group displayed increased sensitivity to FA-induced uncoupling (p = 0.011) compared with muscle from the UT group, and this was ass...Continue Reading

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Jul 23, 2016·Nature Reviews. Endocrinology·Matthijs K C HesselinkPatrick Schrauwen
Sep 7, 2016·Diabetologia·Patrick Schrauwen, Wouter D van Marken Lichtenbelt
Nov 25, 2018·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Jefferson C FrisbeeRobert W Wiseman
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Jun 5, 2019·Journal of Applied Physiology·Pierre-Emmanuel Tardo-DinoAlexandra Malgoyre
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Sep 12, 2020·International Journal of Molecular Sciences·Konstantin N BelosludtsevMikhail V Dubinin
May 19, 2019·Cellular and Molecular Life Sciences : CMLS·Raid B NisrHarinder S Hundal
Jul 25, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xiao-Wen DingJeganathan Ramesh Babu
Aug 19, 2021·Physiological Reports·Pierre-Emmanuel Tardo-DinoAlexandra Malgoyre

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Methods Mentioned

BETA
biopsy
transfection
acetylation

Software Mentioned

Sigmaplot
SPSS
GraphPad Prism

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