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 KIn and Kout 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-[4C]-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), KIn, and Kout (n = 4) were similar to baseline. During SRIF-induced hypoinsulinemia (insulin <15 pM, n = 4) WBGU was close to 0, and FGU, KIn, and Kout 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 ixmol · 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. KIn 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(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 Kln were positively correlated (r = 0.88, P < 0.01). Kout 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, n and uptake of glucose in a parallel fashion, whereas SRIF-induced acute hypoinsulinemia does not seem to affect transmembrane transport or uptake of glucose.

[1]  D. R. Coles,et al.  The source of blood samples withdrawn from deep forearm veins via catheters passed upstream from the median cubital vein , 1958, The Journal of physiology.

[2]  K. Zierler,et al.  THEORY OF THE USE OF ARTERIOVENOUS CONCENTRATION DIFFERENCES FOR MEASURING METABOLISM IN STEADY AND NON-STEADY STATES. , 1961, The Journal of clinical investigation.

[3]  R. S. Dillon Importance of the Hematocrit in Interpretation of Blood Sugar , 1965, Diabetes.

[4]  G. F. Baker,et al.  The asymmetry of the facilitated transfer system for hexoses in human red cells and the simple kinetics of a two component model , 1973, The Journal of physiology.

[5]  M. Caldwell,et al.  The Effect of Somatostatin on Glucose Uptake and Production by Rat Tissues in Vitro , 1977, Diabetes.

[6]  Classification and Diagnosis of Diabetes Mellitus and Other Categories of Glucose Intolerance , 1979, Diabetes.

[7]  G. Holman,et al.  Symmetrical kinetic parameters for 3-O-methyl-D-glucose transport in adipocytes in the presence and in the absence of insulin. , 1981, Biochimica et biophysica acta.

[8]  R. DeFronzo,et al.  The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization , 1981, Diabetes.

[9]  R. DeFronzo,et al.  Regulation of Splanchnic and Peripheral Glucose Uptake by Insulin and Hyperglycemia in Man , 1983, Diabetes.

[10]  R. Bergman,et al.  Extrapancreatic effect of somatostatin infusion to increase glucose clearance. , 1984, The American journal of physiology.

[11]  J A Jacquez,et al.  Red blood cell as glucose carrier: significance for placental and cerebral glucose transfer. , 1984, The American journal of physiology.

[12]  R. DeFronzo,et al.  Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. , 1985, The Journal of clinical investigation.

[13]  C Cobelli,et al.  Effect of insulin on the distribution and disposition of glucose in man. , 1985, The Journal of clinical investigation.

[14]  B. Capaldo,et al.  Direct evidence for a stimulatory effect of hyperglycemia per se on peripheral glucose disposal in type II diabetes. , 1986, The Journal of clinical investigation.

[15]  J B Bassingthwaighte,et al.  Multiple tracer dilution estimates of D- and 2-deoxy-D-glucose uptake by the heart. , 1986, The American journal of physiology.

[16]  A. Baron,et al.  Somatostatin Does Not Increase Insulin-Stimulated Glucose Uptake in Humans , 1987, Diabetes.

[17]  E. Barrett,et al.  Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man. , 1987, The Journal of clinical investigation.

[18]  E. Richter,et al.  Kinetics of glucose transport in rat muscle: effects of insulin and contractions. , 1987, The American journal of physiology.

[19]  H. Yki-Järvinen,et al.  Kinetics of glucose disposal in whole body and across the forearm in man. , 1987, The Journal of clinical investigation.

[20]  R. DeFronzo,et al.  Hyperglucagonemia and insulin-mediated glucose metabolism. , 1987, The Journal of clinical investigation.

[21]  C Bogardus,et al.  No accumulation of glucose in human skeletal muscle during euglycemic hyperinsulinemia. , 1988, The American journal of physiology.

[22]  G. Dohm,et al.  An in vitro human muscle preparation suitable for metabolic studies. Decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects. , 1988, The Journal of clinical investigation.

[23]  A. Baron,et al.  Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. , 1988, The American journal of physiology.

[24]  M. Birnbaum,et al.  Pretranslational suppression of an insulin-responsive glucose transporter in rats with diabetes mellitus. , 1989, Science.

[25]  J. Flier,et al.  Regulation of glucose transporter-specific mRNA levels in rat adipose cells with fasting and refeeding. Implications for in vivo control of glucose transporter number. , 1989, The Journal of clinical investigation.

[26]  C Cobelli,et al.  A compartmental model to quantitate in vivo glucose transport in the human forearm. , 1989, The American journal of physiology.

[27]  A. Carruthers,et al.  Facilitated diffusion of glucose. , 1990, Physiological reviews.

[28]  L. Groop,et al.  Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans. , 1990, The American journal of physiology.

[29]  M. Laakso,et al.  Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. , 1990, The Journal of clinical investigation.

[30]  M. Laakso,et al.  Kinetics of Insulin-Mediated and Non-Insulin-Mediated Glucose Uptake in Humans , 1990, Diabetes.

[31]  P. Pilch,et al.  Regulation of Glucose-Transporter Function , 1990, Diabetes Care.

[32]  C. Palombo,et al.  Impaired Insulin Action on Skeletal Muscle Metabolism in Essential Hypertension , 1991, Hypertension.