TY - JOUR
T1 - Athletes feature greater rates of muscle glucose transport and glycogen synthesis during lipid infusion
AU - Phielix, Esther
AU - Begovatz, Paul
AU - Gancheva, Sofiya
AU - Bierwagen, Alessandra
AU - Kornips, Esther
AU - Schaart, Gert
AU - Hesselink, Matthijs K. C.
AU - Schrauwen, Patrick
AU - Roden, Michael
N1 - Funding Information:
The German Diabetes Center is funded by the BMG and the Ministry of Culture and Science of the State North Rhine-Westphalia. This study was also supported in part by grants from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.), from the German Research Foundation (DFG) through the Collaborative Research Center SFB 1116 (Master switches in cardiac ischemia), and from the Schmutzler Stiftung. The funders had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to publish the manuscript.
Publisher Copyright:
© 2019 American Society for Clinical Investigation. All rights reserved.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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 C-13/P-31 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 (Delta Rd: 25 +/- 3 vs.17 +/- 3 mu mol/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] x h, P = n.s.) but tended to decrease by 36% in sedentary humans (1.7 +/- 0.4 vs.1.1 +/- 0.1 [mmol/L] x 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 mu mol/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.
AB - 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 C-13/P-31 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 (Delta Rd: 25 +/- 3 vs.17 +/- 3 mu mol/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] x h, P = n.s.) but tended to decrease by 36% in sedentary humans (1.7 +/- 0.4 vs.1.1 +/- 0.1 [mmol/L] x 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 mu mol/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.
KW - FREE FATTY-ACIDS
KW - INDUCED INSULIN-RESISTANCE
KW - HUMAN SKELETAL-MUSCLE
KW - PROLONGED SEVERE EXERCISE
KW - OXIDATIVE CAPACITY
KW - GLUT4 EXPRESSION
KW - SENSITIVITY
KW - PHOSPHORYLATION
KW - METABOLISM
KW - DIACYLGLYCEROLS
U2 - 10.1172/jci.insight.127928
DO - 10.1172/jci.insight.127928
M3 - Article
C2 - 31672941
SN - 2379-3708
VL - 4
JO - JCI INSIGHT
JF - JCI INSIGHT
IS - 21
M1 - 127928
ER -