Quantitative measurement of gluconeogenesis from isobutyrate in sheep

Experiments with continuous infusion of [14C] isobutyrate and single injection of [3H] glucose were performed in two sheep under fed and fasted conditions in order to investigate the contribution of isobutyrate to glucose synthesis. The pool size, total entry and irreversible loss of glucose in the fed sheep were 2.8 mmol/kg0.75, 1.70 and 1.43 mmol/h per kg0.75. After 72-h fasting these parameters decreased about 40% but recycling of glucose carbon increased from 16 to 38% of the total entry rate. Isobutyrate infused intravenously at a rate of 3.5 mmol/h contributed to a minimum of 3-5% of glucose entry indicating that at least 40-60% of the infused isobutyrate was used for net glucose synthesis. The efficiency of the glucogenic and energetic use of isobutyrate as compared to propionate is discussed.