In vivo resistance to the action of insulin on gludose uptake has been documented during puberty. To test the hypothesis that the glucose-fatty acid cycle, as proposed by Randle et al. (Randle PJ, Garland PB, Hales CN, Nemsholme EA: The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785-789, 1963), may be responsible for this phenomenon, we studied nine prepubertal (Tanner I), nine pubertal (Tanner II-IV), and five young adult healthy subjects. The rate of lipolysis was measured with [d-5]glycerol tracer during basal state and during a stepwise hyperinsulinemic (10 and 40 mU . m(-2) . min(-1))-euglycemic clamp. The rates of insulin-stimulated glucose disposal (R(d)) were measured during the clamp, whereas glucose and fat oxidation were measured by using indirect respiratory calorimetry. Basal glycerol rate of appearance (R(a); Lipolysis) and fat oxidation were similar between prepubertal and pubertal subjects but higher than adults when the data were expressed per kilogram body weight or per kilogram fat-free mass (FI?lI; glycerol R(a): 2.5 +/- 0.2, 2.6 +/- 0.2 vs. 1.6 +/- 0.2 mu mol . min(-1) . kg FFM(-1), P < 0.05; fat oxidation: 4.4 +/- 0.6, 4.8 +/- 0.3 vs. 3.2 +/- 0.6 mu mol . min(-1) . kg FFM(-1), P < 0.05). However, when expressed for total body, glycerol R(a) and fat oxidation mere higher in pubertal versus prepubertal and adult subjects. Insulin-like growth factor I (IGF-I) levels correlated with total-body lipolysis (r = 0.52, P = 0.006) and with total lipid oxidation (r = 0.44, P = 0.016) at baseline. During the low-rate insulin clamp, glycerol R(a) and fat oxidation were higher in pubertal versus adult subjects (1.5 +/- 0.2 vs. 0.9 +/- 0.1 mu mol . min(-1) . kg FFM(-1), P = 0.04, and 3.7 +/- 0.4 vs. 2.2 +/- 0.4 mu mol . min kg FFM(-1), P = 0.03, respectively). During the high-rate insulin clamp, fat oxidation was significantly higher in pubertal (1.7 +/- 0.3) versus prepubertal (0.7 +/- 0.2) versus adult subjects (0.4 +/- 0.2 mu mol . min kg FFM(-1)), and IGF-I levels correlated positively with total-body lipid oxidation (r = 0.72, P ( 0.001). Insulin-stimulated total and nonoxidative R(d) were significantly lower in pubertal subjects compared with prepubertal and adult subjects (total R(d),
