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 dispos al were explored in three groups of seven normal subjects. Group 1 was subm itted to a euglycemic hyperinsulinemic clamp (similar to 100 mu U/ml) after both a 12-h and a 4-day fast. The combined use of [3-H-3]-and [U-C-14] glu cose allowed us to demonstrate that fasting inhibits, by similar to 50%, gl ucose disposal, glycolysis, glucose oxidation, and glycogen synthesis via t he direct pathway. In group 2, in which the clamp glucose disposal during f asting 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 el evation of insulin (similar to 2,800 mu U/ml), but in this case, both glyco gen synthesis and nonoxidative glycolysis participated in the rise in nonox idative glucose disposal. In all groups, the reduction in total carbohydrat e oxidation (indirect calorimetry) induced by fasting markedly exceeded the reduction in circulating glucose oxidation, suggesting that fasting also i nhibits intracellular glycogen oxidation. Thus prior fasting favors glycoge n retention by three mechanisms: 1) stimulation of glycogen synthesis via t he direct pathway; 2) preferential inhibition of oxidative rather than nono xidative glycolysis, thus allowing carbon conservation for glycogen synthes is via the indirect pathway; and 3) suppression of intracellular glycogen o xidation.