Kinetics of Insulin-Mediated and Non-Insulin-Mediated Glucose Uptake in Humans

The kinetics of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU) in humans have not been well defined. We used the glucose-clamp technique to measure rates of wholebody and leg muscle glucose uptake in six healthy lean men during hyperinsulinemia (∼460 pM) to study IMGU and during somatostatin-induced insulinopenia to study NIMGU at four glucose levels (4.5, 9,12, and 21 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference [A-V_G] × blood flow). With this approach, we found that, during hyperinsulinemia, both whole-body and leg glucose uptake increased in a curvilinear fashion at every glucose level, the highest glucose uptake values obtained being 139 ± 17 μmol · kg⁻¹ · min⁻¹ and 3656 ± 931 μmol · min⁻¹ · leg⁻¹, respectively. Leg blood flow increased twofold from 6.0 ± 1.7 to 11.7 ± 3.1 dl/min (P < 0.01) over the range of glucose and was correlated with whole-body glucose uptake (r = 0.55, P < 0.005). Leg muscle glucose extraction, independent of changes in blood flow, which is reflected by the A-VG, saturated over the range of glucose (1.28 ± 0.12, 2.22 ± 0.30, 2.92 ± 0.42, 3.02 ± 0.41 mM, NS between last 2 values) with a halfmaximal effective glucose concentration (EGS0) of 5.3 ± 0.4 mM. During insulinopenia, both whole-body and leg glucose uptake increased in a near-linear fashion; however, glucose uptake remained significantly lower than that seen with insulin stimulation, the highest glucose uptake values obtained being 22 ± 2 μmol · kg⁻¹ · min⁻¹ and 260 ± 34 μmol · min⁻¹ · leg1, respectively. Leg blood flow was unchanged from the basal value (4.15 ± 0.63 dl/min) over the range of glucose studied, and A-VG increased at all glucose levels: 0.094 ± 0.010, 0.28 ± 0.03, 0.38 ± 0.04, and 0.59 ± 0.03 mM (P < 0.05 between any 2 consecutive values), with an EG₅₀ of 10.0 ± 0.4 mM (P < 0.001 vs. IMGU). We conclude that 1) insulin increases the capacity for muscle A-V_Q approximately fivefold; 2) muscle IMGU, independent of blood flow, displays an EG₅₀ similar to the K_m characteristic of the glucose-transport system (∼5–6 mM); 3) in contrast, NIMGU is a low-affinity glucoseuptake system; and 4) blood flow to insulin-sensitive tissue increases with insulin and glucose infusions and is an important determinant of the rate of in vivo glucose uptake.