Effect of glucose load and of insulin on the metabolism of glucose and of palmitate in sheep.

1. Simultaneous measurements of the entry rates of palmitate and glucose have been made in Merino sheep (wethers), starved for 24hr., by using constant infusions of [9,10-(3)H(2)]palmitate and [U-(14)C]glucose. 2. The infusion of glucose into the peripheral circulation of the sheep lowered the endogenous entry of both glucose and palmitate. Since palmitate is roughly metabolically representative of the free fatty acid fraction, there was no marked change in the calories available to the sheep. 3. The infusion of insulin into either the peripheral or portal circulation increased the uptake of glucose and decreased the uptake of palmitate by the tissues of the sheep. 4. The infusion of insulin into the peripheral circulation produced a depression in glucose entry after about 80min., whereas the infusion of insulin into the portal circulation produced an almost immediate depression in glucose entry. 5. The hypoglycaemia produced gave rise to an increase in free fatty acid production followed by an increase in glucose production. 6. No direct effect of insulin on the metabolism of free fatty acids has been demonstrated by the techniques used. The effect of insulin on the metabolism of free fatty acids is apparently mediated through its effect on glucose metabolism.