The role of fractional glucose extraction in the regulation of splanchnic glucose metabolism in normal and diabetic man

In order to express in equivalent terms seemingly divergent results obtained with isotopic tracer studies as compared to hepatic venous catheter studies on the role of the liver in the metabolism of oral glucose, our previously published studies using the hepatic venous catheter technique in normals and diabetics given intravenous and/or oral glucose were analyzed with respect to the splanchnic fractional extraction of glucose, total splanchnic glucose influx, and the proportion of total glucose metabolism accounted for by net splanchnic glucose uptake. In normal subjects during extreme hyperinsulinemia (plasma insulin, 500–1,200 μU/ml) induced by i.v. insulin while maintaining the blood glucose concentration at basal levels (insulin clamp), total glucose metabolism rose to 10.5 ± 0.9 mg/min · kg, while splanchnic fractional extraction of glucose was 4.2 ± 1.1%, and net splanchnic glucose uptake accounted for only 5 ± 2% of total glucose turnover. During hyperglycemic (blood glucose, 200 mg/dl) hyperinsulinemia induced by i.v. glucose, net splanchnic glucose uptake was twice that observed with euglycemic hyperinsulinemia, and the proportion of total glucose metabolism occurring in the splanchnic bed rose to 14 ± 4%. These increments were due entirely to a rise in splanchnic glucose influx since the fractional extraction (3.4 ± 0.5%) remained unchanged from that observed with euglycemic hyperinsulinemia. After oral glucose (100 g), splanchnic glucose influx was comparable to hyperglycemic hyperinsulinemia induced with i.v. glucose, but splanchnic fractional extraction rose to 13.1 ± 1.9% (p < 0.001 versus i.v. glucose), a value comparable to that observed with isotopic studies of oral glucose metabolism. Total glucose turnover was, however, 30% lower than after i.v. insulin (p < 0.01), so that net splanchnic glucose uptake accounted for 54 ± 5% of total glucose metabolism. In maturity-onset diabetics, after 100 g oral glucose splanchnic glucose influx was 69% greater than in controls (p < 0.001), but net splanchnic glucose uptake was 44% below controls (2.3 ± 0.5 versus 4.1 ± 0.5 mg/min · kg, p < 0.02). This reduction in glucose uptake could be accounted for by a splanchnic fractional extraction ratio (4.7 ± 1.4%) that was 64% lower than in controls given oral glucose (p < 0.001). It is concluded that: (1) in normal subjects, the ability of the splanchnic area to extract circulating glucose (as reflected by the splanchnic fractional extraction) is 2–3-fold greater after oral glucose than after intravenous glucose; (2) the rise in splanchnic fractional extraction to levels of 13% in association with only moderate increases in total glucose turnover fully accounts for the predominance of the splanchnic area in the metabolism of oral as compared to intravenous glucose; and (3) in maturity-onset diabetics, oral glucose fails to induce a rise in splanchnic fractional extraction of glucose comparable to that observed in normal subjects.