Basal plasma insulin levels exert a qualitative but not quantitative effect on glucose-mediated glucose uptake

We assessed the effect of hyperglycemia on glucose uptake in the presence of normal basal insulin levels or somatostatin-induced hypoinsulinemia in seven normal volunteers during a 200-min hyperglycemic clamp (+9 mmol/l) carried out with [3-³H]glucose and indirect calorimetry. Hyperglycemia increased glucose uptake to 22.4 ± 2.6 and 21.3 ± 1.6 μmol · kg^-1 · min^-1 with and without insulin replacement, respectively. Normoinsulinemia increased glucose oxidation (Δ = +4.5 ± 0.6 μmol · kg^-1 · min^-1) and nonoxidative glucose metabolism (Δ = +5.2 ± 1.7 μmol · kg^-1 · min^{- 1}), whereas with insulinopenia, glucose oxidation did not change (Δ = -0.3 ± 0.6 μmol · kg ^-1 · min^-1), and nonoxidative glucose metabolism increased (Δ = +8.7 ± 0.8 μmol · kg^-1 · min^-1). Nonoxidative glucose metabolism was higher during insulinopenic (13.5 ± 1.8 μmol · kg^-1 · min^-1) than normoinsulinemic hyperglycemia (9.8 ± 2.7 μmol · kg^-1 min^-1; p < 0.01). Plasma FFA concentration and lipid oxidation were higher with insulinopenia. Blood lactate and alanine concentrations were greater with normoinsulinemia. In conclusion: 1) hyperglycemia promotes glucose uptake by stimulating both nonoxidative and oxidative glucose disposal; 2) the ability of hyperglycemia to enhance total body glucose uptake is similar with and without normoinsulinemia; 3) although acute insulinopenia does not impair the ability of hyperglycemia to stimulate glucose uptake, it plays a critical role in determining the intracellular metabolic fate of glucose taken up in response to hyperglycemia.