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A B S T R A C T Transport of free fatty acids from the blood into the splanchnic region and their conversion to triglycerides of very low density lipoproteins, together with estimates of splanchnic oxidation of free fatty acids to ketones and to carbon dioxide and water, have been made in the postabsorptive state in seven normolipemic subjects, six with primary endogenous hyperlipemia and one each with primary dysbetalipoproteinemia and mixed hyperlipemia. Net systemic transport of free fatty acids into the blood was the same in normolipemic and hyperlipemic groups, but a greater fraction was taken up in the splanchnic region in the latter. Transport into the blood in very low density lipoproteins of triglyceride fatty acids derived from free fatty acids was proportional and bore the same relationship to splanchnic uptake of free fatty acids in the two groups. In normolipemic subjects, near equilibration of specific activities after 4 hr infusion of palmitate-1-"C showed that almost all triglyceride fatty acids of very low density lipoproteins and acetoacetate were derived from free fatty acids taken up in the splanchnic region. In the hyperlipemic subjects, equilibration of free fatty acidcarbon with acetoacetate was almost complete, but not with triglyceride fatty acids, owing at least in part to increased pool size. Comparison of the rate of equilibraPortions of this work were presented at the Deuel Conference on Lipids, Carmel, Calif., 21 February 1968 (1) tion of triglyceride fatty acids-'4C with rate of inflow transport from the splanchnic region, together with other data, indicated that most of the circulating triglyceride fatty acids of very low density lipoproteins in hyperlipemic subjects were also derived from free fatty acids. Although mean inflow transport of triglyceride fatty acids was greater in the hyperlipemic subjects, it correlated poorly with their concentration and it appeared that efficiency of mechanisms for extrahepatic removal must be a major determinant of the concentration of triglycerides in blood plasma of the normolipemic as well as the hyperlipemic subjects. Estimates of splanchnic respiratory quotient supported the concept that oxidation of free fatty acids accounts for almost all of splanchnic oxygen consumption in the postabsorptive state. Splanchnic oxygen consumption was greater in the hyperlipemics, but fractional oxidation of free fatty acids to ketones was higher in normolipemic subjects. Calculations of splanchnic balance indicate that a larger fraction of free fatty acids was stored in lipids of splanchnic tissues in the hyperlipemics. No differences were found between the two groups in net splanchnic transport of glucose, lactate, or glycerol.

Studies comparing glucose tolerance in the morning vs. that in the evening have suggested that time of day may influence glucose regulation. To examine the variation in glucose tolerance throughout the 24-h span, normal subjects were given an iv glucose infusion at a constant rate of either 5 or 8 g/kg.24 h during 30 h, and plasma levels of insulin and glucose were measured at 15-min intervals for the last 24 h of the infusion. The timing of initiation of the infusion was varied to differentiate effects of time of day from effects of duration of the infusion. A nocturnal elevation of glucose levels, culminating around midsleep and corresponding to an increase of about 15% above daytime levels, was observed in all subjects. The timing of this nocturnal maximum was not dependent on the rate of the infusion or on the time elapsed since the beginning of the infusion. Insulin levels did not show a consistent diurnal pattern. Both insulin and glucose exhibited large ultradian oscillations recurring at 100- to 150-min intervals. The amplitude of these oscillations increased with the rate of glucose infusion. These ultradian oscillations of glucose and insulin levels were temporally correlated, with a tendency for glucose pulses to lead insulin pulses by 15-30 min. These results demonstrate in normal subjects the existence of a diurnal variation in glucose tolerance distinct from the dawn phenomenon observed in diabetic subjects and indicate that spontaneous 100- to 150-min oscillations in peripheral glucose and insulin levels characterize stimulated pancreatic function, with the amplitude of the oscillations being dependent on the size of the stimulus.

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To evaluate the effects of short-term starvation on gastric emptying in normal and obese subjects, the relationship between gastric emptying and oral glucose tolerance, and the mechanisms responsible for the delay in the systemic appearance of oral glucose observed after short-term fasting, we determined the effects of a 4-day fast on 1) gastric emptying and oral glucose tolerance in normal subjects and 2) gastric emptying in obese patients. Gastric emptying of 75 g glucose (320 ml) labeled with 99mTc colloid was measured in 12 healthy volunteers and 11 obese subjects after 12-h and 4-day fasts. In seven other obese subjects, the effect of a 4-day fast on gastric emptying of 320 ml normal saline was quantified. Gastric emptying of glucose was slower after the 4-day than after the overnight fast in both normal (P = 0.02) and obese (P < 0.001) subjects, with no difference between the two groups. In normal subjects, the rate of gastric emptying was related directly to the rise in plasma glucose at 30 min (r = 0.60; P < 0.05) but inversely to the plasma glucose at 180 min (r = -0.64; P < 0.02). In the obese subjects, gastric emptying of saline was not affected by fasting. These observations indicate that 1) gastric emptying of glucose is retarded by a 4-day fast, 2) the changes in gastric emptying reported in obesity may reflect different patterns of prior nutrient intake, and 3) delay in gastric emptying accounts for the slower systemic appearance of glucose after fasting.