FREE FATTY-ACIDS;
INDUCED INSULIN-RESISTANCE;
HUMAN SKELETAL-MUSCLE;
PROLONGED SEVERE EXERCISE;
OXIDATIVE CAPACITY;
GLUT4;
EXPRESSION;
SENSITIVITY;
PHOSPHORYLATION;
METABOLISM;
DIACYLGLYCEROLS;
D O I:
10.1172/jci.insight.127928
中图分类号:
R-3 [医学研究方法];
R3 [基础医学];
学科分类号:
1001 ;
摘要:
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.
机构:
Univ Virginia Hlth Syst, Dept Med, Div Endocrinol, Charlottesville, VA USAUniv Virginia Hlth Syst, Dept Med, Div Endocrinol, Charlottesville, VA USA
Eggleston, Emma M.
Jahn, Linda A.
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机构:
Univ Virginia Hlth Syst, Dept Med, Div Endocrinol, Charlottesville, VA USAUniv Virginia Hlth Syst, Dept Med, Div Endocrinol, Charlottesville, VA USA
Jahn, Linda A.
Barrett, Eugene J.
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h-index: 0
机构:
Univ Virginia Hlth Syst, Dept Med, Div Endocrinol, Charlottesville, VA USAUniv Virginia Hlth Syst, Dept Med, Div Endocrinol, Charlottesville, VA USA