Glucose transport in human skeletal muscle: The in vivo response to insulin

Transmembrane glucose transport plays a key role in determining insulin sensitivity. We have measured in vivo WBGU, FGU, and K_in and K_out of 3-O-methyl-D-glucose in forearm skeletal muscle by combining the euglycemic clamp technique, the forearm-balance technique, and a novel dual-tracer (1-[³H]-L-glucose and 3-O-[¹⁴C]-methyl-D-glucose) technique for measuring in vivo transmembrane transport. Twenty-seven healthy, lean subjects were studied. During saline infusion, insulin concentration, FGU (n = 6), K_in, and K_out, (n = 4) were similar to baseline. During SRIF-induced hypoinsulinemia (insulin < 15 pM, n = 4) WBGU was close to 0, and FGU, K_in, and K_out were unchanged from basal (insulin = 48 pM) values. During insulin clamps at plasma insulin levels of ∼180 (n = 4), ∼420 (n = 5), ∼3000 (n = 4), and ∼9500 pM (n = 4), WBGU was 14.2 ± 1.3, 34.2 ± 4.1 (P < 0.05 vs. previous step), 55.8 ± 1.8 (P < 0.05 vs. previous step), and 56.1 ± 6.3 μmol · min^-1 · kg^-1 of body weight (NS vs. previous step), respectively. Graded hyperinsulinemia concomitantly increased FGU from a basal value of 4.7 ± 0.5 μmol · min^-1 · kg^-1 up to 10.9 ± 2.3 (P < 0.05 vs. basal value), 26.6 ± 4.5 (P < 0.05 vs. previous step), 54.8 ± 4.3 (P < 0.05 vs. previous step), and 61.1 ± 10.8 μmol · min^-1 · kg^-1 of forearm tissues (NS vs. previous step), respectively. K_in of 3-O-methyl-D-glucose in forearm skeletal muscle was increased by hyperinsulinemia from a basal value of 6.6 · 10^-2 ± 0.38 10^-2 to 10.0 · 10^-2 ± 1.4 · 10^-2 (p < 0.05 vs. baseline), 17.2 · 10^-2 ± 2.2 · 10^-2 (P < 0.05 vs. previous step), 26.3 · 10^-2 ± 1.8 · 10^-2 (P < 0.05 vs. previous step), and 29.8 · 10^-2 ± 5.3 · 10^-2 · min^-1 (NS vs. previous step), respectively. FGU and K_in were positively correlated (r = 0.88, P < 0.01). K_out of 3-O-methyl-D-glucose did not change from the basal value at the lowest insulin dose (3.9 · 10^-2 ± 1.1 · 10^-2 vs. 3.8 · 10^-2 ± 0.33 · 10^-2 · 10^-2 · min^-1, NS), but rose significantly at the following insulin steps to 6.1 · 10^-2 ± 0.8 · 10^-2, 6.9 · 10^-2 ± 0.5 · 10^-2, and 11.9 · 10^-2 ± 0.3 · 10^-2 · min^-1 (P < 0.05 for all three vs. baseline). Thus, in human skeletal muscle, in vivo, insulin stimulates K_in and uptake of glucose in a parallel fashion, whereas SRIF-induced acute hypoinsulinemia does not seem to affect transmembrane transport or uptake of glucose.