BACKGROUND Insulin resistance results from impaired skeletal muscle glucose transport/phosphorylation, linked to augmented lipid availability. Despite greater intramuscular lipids, athletes are highly insulin sensitive, which could result from higher rates of insulin-stimulated glycogen synthesis or glucose transport/phosphorylation and oxidation. Thus, we examined the time course of muscle glycogen and glucose-6-phosphate concentrations during low and high systemic lipid availability.METHODS Eight endurance-trained and 9 sedentary humans (VO2 peak: 56 ± 2 vs. 33 ± 2 mL/kg/min, P < 0.05) underwent 6-hour hyperinsulinemic-isoglycemic clamp tests with infusions of triglycerides or saline in a randomized crossover design. Glycogen and glucose-6-phosphate concentrations were monitored in vastus lateralis muscles using 13C/31P magnetic resonance spectroscopy.RESULTS Athletes displayed a 25% greater (P < 0.05) insulin-stimulated glucose disposal rate (Rd) than sedentary participants. During Intralipid infusion, insulin sensitivity remained higher in the athletes (ΔRd: 25 ± 3 vs. 17 ± 3 μmol/kg/min, P < 0.05), supported by higher glucose transporter type 4 protein expression than in sedentary humans. Compared to saline infusion, AUC of glucose-6-phosphate remained unchanged during Intralipid infusion in athletes (1.6 ± 0.2 mmol/L vs. 1.4 ± 0.2 [mmol/L] × h, P = n.s.) but tended to decrease by 36% in sedentary humans (1.7 ± 0.4 vs. 1.1 ± 0.1 [mmol/L] × h, P < 0.059). This drop was accompanied by a 72% higher rate of net glycogen synthesis in the athletes upon Intralipid infusion (47 ± 9 vs. 13 ± 3 μmol/kg/min, P < 0.05).CONCLUSION Athletes feature higher skeletal muscle glucose disposal and glycogen synthesis during increased lipid availability, which primarily results from maintained insulin-stimulated glucose transport with increased myocellular glucose-6-phosphate levels for subsequent glycogen synthesis.TRIAL REGISTRATION ClinicalTrials.gov NCT01229059.FUNDING German Federal Ministry of Health (BMG).
Esther Phielix, Paul Begovatz, Sofiya Gancheva, Alessandra Bierwagen, Esther Kornips, Gert Schaart, Matthijs K. C. Hesselink, Patrick Schrauwen, Michael Roden
Plasma FFA and insulin sensitivity during saline or Intralipid infusion.