GLUCOSE-TRANSPORT IN HUMAN SKELETAL-MUSCLE - THE INVIVO 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 3-0-methyl-D-glucose in forearm skeletal muscle by combining the euglycemic clamp technique, the forearm-balance technique, and a novel dual-tracer (1-[H-3]-L-glucose and 3-0-[C-14]-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 approximately 180 (n = 4), approximately 420 (n = 5), approximately 3000 (n = 4), and approximately 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 mumol . 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 mumol . 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 mumol - 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 3-0-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.