Although it is an established concept that the liver is important in the dispositionof glucose, the quantitative contribution of the splanchnic and peripheral tissues, respectively,to the disposal of an oral glucose load is still controversial. In the present investigation, we have employed the hepatic venous catheter technique in combination with a double-tracer approach(in which the glucose pool is labeled with 3H-glucose and the oral glucose load is labeled with 14C-glucose) to quantitate the four determinants of oral glucose tolerance: rate of oral glucose appearance, splanchnic glucose uptake, peripheral glucose uptake, and suppression of hepatic glucose production. Studies were carried out in 11 normal volunteers in the overnight-fasted state and for 3.5 h after the ingestion of glucose (1 g/kg body wt; range, 55–93 g).
In the postabsorptive state, the rate of endogenous (hepatic) glucose production, evaluated from the 3H-glucose infusion, was 2.34 ± 0.06 mg/min · kg. Glucose ingestion was accompanied by a prompt reduction of endogenous glucose output, which reached a nadir of 0.62 ± 0.23 mg/min kg at 45 min and remained suppressed after 3.5 h (0.85 ±0.22 mg/ min · kg). The average inhibition of hepatic glucose output during the absorptive period was 53 ± 5%. The appearance of ingested glucose in arterial blood, as derived from the 14C-glucose measurements after correction for recycling 14C radioactivity, reached a peak after 15–30 min, and 14C-glucose continued to enter the systemic circulation throughout the observation period. The rate of appearance of ingested glucose was 2.47 ± 0.45 mg/min kg at 3.5 h. A total of 73 ± 4% of the oral load was recovered in the systemic circulation within 3.5 h. The cumulative net output of glucose from the splanchnic area, measured directly with the hepatic vein catheter technique, was 46 ± 5 g over 3.5 h. This net splanchnic glucose balance resulted from the appearance of 50 ± 5 g of the glucose load plus a residual hepatic production of 15 ± 2 g, minus a splanchnic glucose uptake of 19 ± 4 g. Splanchnic fractional extraction of glucose (basal = 2.7 ± 0.7%) failed to increase in response to glucose ingestion. Splanchnic glucose uptake, however, was significantly (P < 0.001) higher during the absorptive period (19 ± 4 g/3.5 h) than in the basal state (5 ± 1 g/3.5 h). Peripheral glucose uptake (48 ± 6 g/3.5 h) was also enhanced by glucose ingestion (P < 0.001 versus a basal value of 27 ± 2 g/3.5 h) and accounted for over 70% of total glucose disposal.
It is concluded that, after the ingestion of a glucose load in healthy subjects: (1) endogenous glucose production is suppressed by approximately 50%, (2) both splanchnic and peripheral uptake of glucose are stimulated, (3) the rise in splanchnic uptake is achieved primarily by augmented glucose availability rather than by increased splanchnic fractional extraction of glucose, and (4) peripheral glucose uptake accounts for the majority Of total glucose disposal.