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Cited by 393Pancreatic function and diabetesDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Management and Research

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

Hovorka, Roman, Shojaee-Moradie, Fariba, Carroll, Paul V., Chassin, Ludovic J., Gowrie, Ian J., Jackson, Nicola C., Tudor, Romulus S., Umpleby, A. Margot +1 more·2002·American Journal of Physiology-Endocrinology and Metabolism
DOI 10.1152/ajpendo.00304.2001
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Abstract

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-(13)C]glucose and 5-10% 3-O-methyl-D-glucose) preceded by a 2-h investigation under basal conditions (5 mg/kg of D-[U-(13)C]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 small middle dot kg(-1) small middle dot 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.

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Crossref · 10.1152/ajpendo.00304.2001

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  • The Hovorka model and the UVAPadova model were originally formulated to represent the physiological behaviour of T1DM individuals, and no modification is necessary for the purpose of the present work.

    “On the contrary, the Hovorka model and the UVAPadova model were originally formulated to represent the physiological behaviour of T1DM individuals, and no modification is necessary for the purpose of the present work.”

    From A comparison among three maximal mathematical models of the glucose-insulin system (2021) · cites this paper as [17]

  • The Hovorka model is well documented.

    “The Hovorka model is the simplest of the three models, well documented and used primarily for the development of control algorithms.”

    From A comparison among three maximal mathematical models of the glucose-insulin system (2021) · cites this paper as [17]

  • The Hovorka model is the simplest of the three models.

    “The Hovorka model is the simplest of the three models, well documented and used primarily for the development of control algorithms.”

    From A comparison among three maximal mathematical models of the glucose-insulin system (2021) · cites this paper as [17]

  • The Hovorka model and the UVAPadova Simulator describe only the glucose metabolism of a subject with type 1 diabetes.

    “While the Hovorka model and the UVAPadova Simulator only describe the glucose metabolism of a subject with type 1 diabetes, the Sorensen model was formulated to simulate the behaviour of both normal and diabetic individuals.”

    From A comparison among three maximal mathematical models of the glucose-insulin system (2021) · cites this paper as [17]

  • The Hovorka model is used primarily for the development of control algorithms.

    “The Hovorka model is the simplest of the three models, well documented and used primarily for the development of control algorithms.”

    From A comparison among three maximal mathematical models of the glucose-insulin system (2021) · cites this paper as [17]

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Authors
Hovorka, R., Shojaee-Moradie, F., Carroll, P. V., Chassin, L. J., Gowrie, I. J., Jackson, N. C., Tudor, R. S., Umpleby, A. M., & Jones, R. H.
Affiliations
  • City, University of London (GB)
  • Department of Diabetes and Endocrinology, GKT School of Medicine, St. Thomas' Hospital, London SE1 7EH, United Kingdom
  • St Thomas' Hospital (GB)
ORCID
Venue
American Journal of Physiology-Endocrinology and Metabolism
Publisher
American Physiological Society
Published
2002-05-01
Volume
282
Issue
5
Pages
E992-E1007
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
DOI
10.1152/ajpendo.00304.2001
OpenAlex
W2001875222
Cited by
393
References
49
Citations by year
2026: 3 · 2025: 9 · 2024: 14 · 2023: 16 · 2022: 12 · 2021: 21 · 2020: 23 · 2019: 16 · 2018: 24 · 2017: 19 · 2016: 22 · 2015: 24 · 2014: 21 · 2013: 15 · 2012: 18
FWCI
5.77
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Open Research (University of Surrey) (submittedVersion)
  • Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
insulin sensitivity, glucose disposal, endogenous glucose production, intravenous glucose tolerance test, 3-O-methylglucose, minimal models, glucose kinetics
MeSH terms
Adult, Blood Glucose, Carbon Isotopes, Glucose, Glucose Tolerance Test, Humans, Insulin, Male, Models, Biological, 3-O-Methylglucose

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