GLUCOSE FATTY-ACID CYCLE OPERATES IN HUMANS AT THE LEVELS OF BOTH WHOLE-BODY AND SKELETAL-MUSCLE DURING LOW AND HIGH PHYSIOLOGICAL PLASMA-INSULIN CONCENTRATIONS

Plasma non-esterified fatty acid concentrations were elevated acutely (Intralipid + heparin infusion) in 14 normal humans in order to study the effects of fatty acids on whole-body basal and insulin-stimulated glucose metabolism, and on activities of skeletal muscle key enzymes. Whole-body glucose metabolism was assessed using [3-H-3]glucose and in direct calorimetry. Biopsies were taken from the vastus lateralis musc le during basal and insulin-stimulated (3 h, 40 mU.m(-2).min(-1)) stea dy-state periods. Total peripheral glucose uptake was unaffected by In tralipid infusion in the basal state, whereas it decreased during Intr alipid infusion in the hyperinsulinemic state (10.7 +/- 0.7 vs 8.7 +/- 0.8 mg.kg(-1) fat-free mass.min(-1), p < 0.02). Intralipid infusion d ecreased whole-body glucose oxidation in the basal state (1.3 +/- 0.2 vs 0.8 +/- 0.1 mg.kg(-1) fat-free mass.min(-1), p < 0.001) and during hyperinsulinemia (3.6 +/- 0.2 vs 1.7 +/- 0.2 mg.kg(-1) fat-free mass.m in(-1) p < 0.001). Whole-body non-olddative glucose uptake increased d uring Intralipid infusion in the basal state and was unaffected in the hyperinsulinemic state. The skeletal muscle pyruvate dehydrogenase ac tivity ratio decreased in the basal state during Intralipid infusion ( 55 +/- 6 vs 43 +/- 5%. p < 0.05), whereas no statistical significant d ecrease in the pyruvate dehydrogenase activity ratio was observed duri ng insulin infusion (57 +/- 8 vs 47 +/- 5% NS). Insulin increased the activity of the active form of pyruvate dehydrogenase on the control d ay, but not during Intralipid infusion. Activities of phosphofructokin ase and glycogen synthase were unaffected by Intralipid infusion. Plas ma glucose concentrations were similar during Intralipid infusion and on the control day, whereas Intralipid infusion increased the muscle g lucose content in the basal state (1.36 +/- 0.09 vs 1.77 +/- 0.12 mmol /kg dry wt, p < 0.05) and in the hyperinsulinemic state (1.23 +/- 0.09 vs 1.82 +/- 0.16 mmol/kg dry wt, p<0.05). Insulin increased the muscl e lactate content on the control day (6.50 +/- 0.95 vs 8.65 +/- 0.77 m mol/kg dry wt, p < 0.05), but not during Intralipid infusion. In concl usion, the glucose-fatty acid cycle operates in humans in vivo at the levels of both whole body and skeletal muscle during both low and high physiological insulin concentrations.