Dietary and Hormonal Effects on Gluconeogenesis and Glycogenesis from Pyruvate-3-¹⁴C, Fructose-U-¹⁴C and Glycerol-2-¹⁴C in the Rat

When a single dose of 0.5 mmole fructose-U-¹⁴C or 1 mmole glycerol-2-¹⁴C was injected intraperitoneally in rats, the radioactivity of the extracellular fluid glucose increased steadily to reach a peak at between 30 and 45 min and then declined, just as was observed previously after injection of 1 mmole pyruvate-3-¹⁴C. Although glucose production from labeled fructose and glycerol in fed rats was 4- to 6-fold higher than that from pyruvate, nevertheless there were further increments in glucose formation from these labeled precursors in 48-hr fasted rats. These findings suggest that major suppression of glucose synthesis by glucose feeding is exerted below triose phosphate on the gluconeogenesis pathway, but that secondary control may be exerted between triose phosphate and hexose. When measured at early periods after injection of precursor, glucose formation from labeled pyruvate was markedly increased by prior treatment of rats with glucagon, catecholamines or guinea pig anti-insulin serum, and these effects were counteracted by insulin. Glucose production from labeled fructose and glycerol also was further increased by glucagon, epinephrine and anti-insulin serum and was counteracted somewhat by insulin; but the already high glucose formation in untreated rats discounted a major effect of these hormones on gluconeogenesis from these precursors. In untreated alloxan-diabetic rats, incorporation of labeled fructose and glycerol into glucose was very high, but incorporation into liver glycogen was very low. After insulin treatment, the proportions in glucose and glycogen were reversed, without appreciable change in total hexose synthesized. These findings confirm a role of insulin in suppressing gluconeogenesis and enhancing glycogenesis; and are in accord with the conception that these processes are regulated physiologically by competitive effects of glucagon and insulin on the level of 3′,5′-cyclic AMP. (Endocrinology86: 1264, 1970)