Phielix 2012 Diabetes
|Phielix E, Meex R, Ouwens DM, Sparks LM, Hoeks J, Schaart G, Moonen-Kornips E, Hesselink MK, Schrauwen P (2012) High oxidative capacity due to chronic exercise training attenuates lipid-induced insulin resistance. Diabetes 61:2472-8.|
Abstract: 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/m(2)) and 10 untrained subjects (age = 21.9 ± 0.9 years; BMI = 22.8 ± 0.6 kg/m(2)) 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.
• Keywords: Lipid-induced insulin resistance (IR), nonoxidative glucose disposal (NOGD), exercise training, glucose
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine Pathology: Diabetes Stress:Mitochondrial disease Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Regulation: Aerobic glycolysis, Substrate Coupling state: OXPHOS