TY - JOUR
T1 - Glucose transport in human skeletal muscle
T2 - The in vivo response to insulin
AU - Bonadonna, R. C.
AU - Saccomani, M. P.
AU - Seely, L.
AU - Zych, K. S.
AU - Ferrannini, E.
AU - Cobelli, C.
AU - DeFronzo, R. A.
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0027463916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027463916&partnerID=8YFLogxK
U2 - 10.2337/diab.42.1.191
DO - 10.2337/diab.42.1.191
M3 - Article
C2 - 8093605
AN - SCOPUS:0027463916
SN - 0012-1797
VL - 42
SP - 191
EP - 198
JO - Diabetes
JF - Diabetes
IS - 1
ER -