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

被引:242
作者
Hovorka, R
Shojaee-Moradie, F
Carroll, PV
Chassin, LJ
Gowrie, IJ
Jackson, NC
Tudor, RS
Umpleby, AM
Jones, RH
机构
[1] City Univ London, Ctr Measurement & Informat Med, Metab Modelling Grp, London EC1V 0HB, England
[2] St Thomas Hosp, GKT Sch Med, Dept Endocrinol & Diabet, London SE1 7EH, England
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2002年 / 282卷 / 05期
关键词
glucose kinetics; compartment modeling; D-[U-C-13] glucose; 3-O-methyl-D-glucose; insulin action; glucose transport; glucose disposal; endogenous glucose production; intravenous glucose tolerance test;
D O I
10.1152/ajpendo.00304.2001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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/m(2)) underwent a 4-h IVGTT (0.3 g/kg glucose enriched with 3-6% D-[U-C-13] glucose and 5-10% 3-O-methyl-D-glucose) preceded by a 2-h investigation under basal conditions (5 mg/kg of D-[U-C-13] 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 x 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.
引用
收藏
页码:E992 / E1007
页数:16
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