CoChat
Sign Up
Cited by 244Pancreatic function and diabetesDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

The DOI matches its Crossref record; 43 of the 45 references it cites were found in a registry or an index.

Insulin Control of Glucose Metabolism in Man

Open access
Insel, Paul A., Liljenquist, John E., Tobin, Jordan D., Sherwin, Robert S., Watkins, Paul, Andres, Reubin, Berman, Mones·1975·Journal of Clinical Investigation
DOI 10.1172/jci108006PMC PMC301852
Open this paper in CoChat — free accountOpen PDF

Abstract

Analyses of the control of glucose metabolism by insulin have been hampered by changes in bloog glucose concentration induced by insulin administration with resultant activation of hypoglycemic counterregulatory mechanisms. To eliminate such mechanisms, we have employed the glucose clamp technique which allows maintenance of fasting blood glucose concentration during and after the administration of insulin. Analyses of six studies performed in young healthy men in the postabsorptive state utilizing the concurrent administration of [14C]glucose and 1 mU/kg per min (40 mU/m2 per min) porcine insulin led to the development of kinetic models for insulin and for glucose. These models account quantitatively for the control of insulin on glucose utilization and on endogenous glucose production during nonsteady states. The glucose model, a parallel three-compartment model, has a central compartment (mass = 68 +/- 7 mg/kg; space of distribution = blood water volume) in rapid equilibrium with a smaller compartment (50 +/- 17 mg/kg) and in slow equilibrium with a larger compartment (96 +/-21 mg/kg). The total plasma equivalent space for the glucose system averaged 15.8 liters or 20.3% body weight. Two modes of glucose loss are introduced in the model. One is a zero-order loss (insulin and glucose independent) from blood to the central nervous system; its magnitude was estimated from published data. The other is an insulin-dependent loss, occurring from the rapidly equilibrating compartment and, in the basal period, is smaller than the insulin-independent loss. Endogenous glucose production averaged 1.74 mg/kg per min in the basal state and enters the central compartment directly. During the glucose clamp experiments plasma insulin levels reached a plateau of 95 +/-8 microU/ml. Over the entire range of insulin levels studied, glucose losses were best correlated with levels of insulin in a slowly equilibrating insulin compartment of a three-compartment insulin model. A proportional control by this compartment on glucose utilization was adequate to satisfy the observed data. Insulin also rapidly decreased the endogenous glucose production to 33% of its basal level (0.58 mg/kg per min), this suppression being maintained for at least 40 min after exogenous insulin infusion was terminated and after plasma insulin concentrations had returned to basal levels. The change in glucose utilization per unit change in insulin in the slowly equilibrating insulin compartment is proposed as a new measure for insulin sensitivity. This defines insulin effects more precisely than previously used measures, such as plasma glucose/plasma insulin concentration ratios. Glucose clamp studies and the modeling of the coupled kinetics of glucose and insulin offers a new and potentially valuable tool to the study of altered states of carbohydrate metabolism.

Overview

Integrity signals

Registry

Crossref · 10.1172/jci108006

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Cited by

Sorted by citations

See all 244

Related

See all

Metadata

Authors
Insel, P. A., Liljenquist, J. E., Tobin, J. D., Sherwin, R. S., Watkins, P., Andres, R., & Berman, M.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1975-05-01
Volume
55
Issue
5
Pages
1057-1066
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci108006
PMC
PMC301852
OpenAlex
W1860443407
Cited by
244
References
45
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 4 · 2014: 3 · 2013: 1 · 2012: 4
FWCI
12.50
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
insulin, glucose metabolism, glucose utilization, endogenous glucose production, insulin sensitivity, glucose kinetics, insulin kinetics, hypoglycemic counterregulation, postabsorptive state, glucose clamp, kinetic modeling, hyperinsulinemic-euglycemic clamp
MeSH terms
Adolescent, Adult, Blood Glucose, Carbon Radioisotopes, Glucose, Glucose Tolerance Test, Humans, Infusions, Intravenous, Insulin, Kinetics, Male, Glucose Clamp Technique, Feedback, Physiological

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review