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Am J Physiol Endocrinol Metab 282: E992-E1007, 2002. First published January 2, 2002; doi:10.1152/ajpendo.00304.2001
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Vol. 282, Issue 5, E992-E1007, May 2002

Partitioning glucose distribution/transport, disposal, and endogenous production during IVGTT

Roman Hovorka1, Fariba Shojaee-Moradie2, Paul V. Carroll2, Ludovic J. Chassin1, Ian J. Gowrie1, Nicola C. Jackson2, Romulus S. Tudor1, A. Margot Umpleby2, and Richard H. Jones2

1 Centre for Measurement and Information in Medicine, City University, London EC1V 0HB; and 2 Department of Diabetes and Endocrinology, GKT School of Medicine, St. Thomas' Hospital, London SE1 7EH, United Kingdom

We have separated the effect of insulin on glucose distribution/transport, glucose disposal, and endogenous production (EGP) during an intravenous glucose tolerance test (IVGTT) by use of a dual-tracer dilution methodology. Six healthy lean male subjects (age 33 ± 3 yr, body mass index 22.7 ± 0.6 kg/m2) underwent a 4-h IVGTT (0.3 g/kg glucose enriched with 3-6% D-[U-13C]glucose and 5-10% 3-O-methyl-D-glucose) preceded by a 2-h investigation under basal conditions (5 mg/kg of D-[U-13C]glucose and 8 mg/kg of 3-O-methyl-D-glucose). A new model described the kinetics of the two glucose tracers and native glucose with the use of a two-compartment structure for glucose and a one-compartment structure for insulin effects. Insulin sensitivities of distribution/transport, disposal, and EGP were similar (11.5 ± 3.8 vs. 10.4 ± 3.9 vs. 11.1 ± 2.7 × 10-2 ml · kg-1 · min-1 per mU/l; P = nonsignificant, ANOVA). When expressed in terms of ability to lower glucose concentration, stimulation of disposal and stimulation of distribution/transport accounted each independently for 25 and 30%, respectively, of the overall effect. Suppression of EGP was more effective (P < 0.01, ANOVA) and accounted for 50% of the overall effect. EGP was suppressed by 70% (52-82%) (95% confidence interval relative to basal) within 60 min of the IVGTT; glucose distribution/transport was least responsive to insulin and was maximally activated by 62% (34-96%) above basal at 80 min compared with maximum 279% (116-565%) activation of glucose disposal at 20 min. The deactivation of glucose distribution/transport was slower than that of glucose disposal and EGP (P < 0.02) with half-times of 207 (84-510), 12 (7-22), and 29 (16-54) min, respectively. The minimal-model insulin sensitivity was tightly correlated with and linearly related to sensitivity of EGP (r = 0.96, P < 0.005) and correlated positively but nonsignificantly with distribution/transport sensitivity (r = 0.73, P = 0.10) and disposal sensitivity (r = 0.55, P = 0.26). We conclude that, in healthy subjects during an IVGTT, the two peripheral insulin effects account jointly for approximately one-half of the overall insulin-stimulated glucose lowering, each effect contributing equally. Suppression of EGP matches the effect in the periphery.

glucose kinetics; compartment modeling; D-[U-13C]glucose; 3-O-methyl-D-glucose; insulin action; glucose transport; glucose disposal; endogenous glucose production; intravenous glucose tolerance test


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