The time-dependent effect of Intralipid infusion on glucose metabolism was examined in seven healthy young subjects who participated in the following three experimental protocols: study I, a 4-h euglycemic insulin clamp (0-240 min) with [3-3H]glucose and indirect calorimetry; study II, a 4-h insulin clamp with Intralipid infusion started at time 0; and study III, a 4-h insulin clamp with Intralipid infusion started at 120 min. When Intralipid infusion was begun at the start of the insulin clamp, the increase in insulin-mediated glucose oxidation was completely inhibited, and the rise in nonoxidative glucose disposal was diminished by 22%. When Intralipid infusion was begun 120 min after the start of the insulin clamp, no inhibitory effect on either glucose oxidation or nonoxidative glucose disposal was observed. The change in lipid oxidation was closely and inversely correlated with the change in glucose oxidation (r =-0.826, P less than 0.001) during studies I-III; no correlation between the change in lipid oxidation and nonoxidative glucose disposal was observed. These results indicate that, in healthy subjects, the metabolic competition between lipid and glucose is very time dependent. Furthermore, mitochondrial oxidative processes are more sensitive and are affected earlier than the cytosolic metabolic pathways, i.e., nonoxidative glucose disposal.
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