Effect of fasting on the intracellular metabolic partition of intravenously infused glucose in humans

The effects of fasting on the pathways of insulin-stimulated glucose disposal were explored in three groups of seven normal subjects. Group 1 was submitted to a euglycemic hyperinsulinemic clamp ( approximately 100 microU/ml) after both a 12-h and a 4-day fast. The combined use of [3-(3)H]- and [U-(14)C]glucose allowed us to demonstrate that fasting inhibits, by approximately 50%, glucose disposal, glycolysis, glucose oxidation, and glycogen synthesis via the direct pathway. In group 2, in which the clamp glucose disposal during fasting was restored by hyperglycemia (155 +/- 15 mg/dl), fasting stimulated glycogen synthesis (+29 +/- 2%) and inhibited glycolysis (-32 +/- 3%) but only in its oxidative component (-40 +/- 3%). Results were similar in group 3 in which the clamp glucose disposal was restored by a pharmacological elevation of insulin ( approximately 2,800 microU/ml), but in this case, both glycogen synthesis and nonoxidative glycolysis participated in the rise in nonoxidative glucose disposal. In all groups, the reduction in total carbohydrate oxidation (indirect calorimetry) induced by fasting markedly exceeded the reduction in circulating glucose oxidation, suggesting that fasting also inhibits intracellular glycogen oxidation. Thus prior fasting favors glycogen retention by three mechanisms: 1) stimulation of glycogen synthesis via the direct pathway; 2) preferential inhibition of oxidative rather than nonoxidative glycolysis, thus allowing carbon conservation for glycogen synthesis via the indirect pathway; and 3) suppression of intracellular glycogen oxidation.