RT Journal Article
SR Electronic
T1 High Oxidative Capacity Due to Chronic Exercise Training Attenuates Lipid-Induced Insulin Resistance
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 2472
OP 2478
DO 10.2337/db11-1832
VO 61
IS 10
A1 Phielix, Esther
A1 Meex, Ruth
A1 Ouwens, D. Margriet
A1 Sparks, Lauren
A1 Hoeks, Joris
A1 Schaart, Gert
A1 Moonen-Kornips, Esther
A1 Hesselink, Matthijs K.C.
A1 Schrauwen, Patrick
YR 2012
UL http://diabetes.diabetesjournals.org/content/61/10/2472.abstract
AB Fat accumulation in skeletal muscle combined with low mitochondrial oxidative capacity is associated with insulin resistance (IR). Endurance-trained athletes, characterized by a high oxidative capacity, have elevated intramyocellular lipids, yet are highly insulin sensitive. We tested the hypothesis that a high oxidative capacity could attenuate lipid-induced IR. Nine endurance-trained (age = 23.4 ± 0.9 years; BMI = 21.2 ± 0.6 kg/m2) and 10 untrained subjects (age = 21.9 ± 0.9 years; BMI = 22.8 ± 0.6 kg/m2) were included and underwent a clamp with either infusion of glycerol or intralipid. Muscle biopsies were taken to perform high-resolution respirometry and protein phosphorylation/expression. Trained subjects had ∼32% higher mitochondrial capacity and ∼22% higher insulin sensitivity (P < 0.05 for both). Lipid infusion reduced insulin-stimulated glucose uptake by 63% in untrained subjects (P < 0.05), whereas this effect was blunted in trained subjects (29%, P < 0.05). In untrained subjects, lipid infusion reduced oxidative and nonoxidative glucose disposal (NOGD), whereas trained subjects were completely protected against lipid-induced reduction in NOGD, supported by dephosphorylation of glycogen synthase. We conclude that chronic exercise training attenuates lipid-induced IR and specifically attenuates the lipid-induced reduction in NOGD. Signaling data support the notion that high glucose uptake in trained subjects is maintained by shuttling glucose toward storage as glycogen.