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Cited by 444Pancreatic function and diabetesDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Management and Research

Quantitative study of insulin secretion and clearance in normal and obese subjects

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Polonsky, K S, Given, B D, Hirsch, L, Shapiro, E T, Tillil, H, Beebe, C, Galloway, J A, Frank, B H +2 more·1988·Journal of Clinical Investigation
DOI 10.1172/jci113338PMC PMC329588
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Abstract

The secretion and hepatic extraction of insulin were compared in 14 normal volunteers and 15 obese subjects using a previously validated mathematical model of insulin secretion and rate constants for C-peptide derived from analysis of individual decay curves after intravenous bolus injections of biosynthetic human C-peptide. Insulin secretion rates were substantially higher than normal in the obese subjects after an overnight fast (86.7 +/- 7.1 vs. 50.9 +/- 4.8 pmol/m2 per min, P less than 0.001, mean +/- SEM), over a 24-h period on a mixed diet (279.6 +/- 24.2 vs. 145.8 +/- 8.8 nmol/m2 per 24 h, P less than 0.001), and during a hyperglycemic intravenous glucose infusion (102.2 +/- 10.8 vs. 57.2 +/- 2.8 nmol/m2 per 180 min, P less than 0.001). Linear regression analysis revealed a highly significant relationship between insulin secretion and body mass index. Basal hepatic insulin extraction was not significantly different in the normal and obese subjects (53.1 +/- 3.8 vs. 51.6 +/- 4.0%). In the normal subjects, fasting insulin did not correlate with basal hepatic insulin extraction, but a significant negative correlation between fasting insulin and hepatic insulin extraction was seen in obesity (r = -0.63, P less than 0.02). This finding reflected a higher extraction in the six obese subjects with fasting insulin levels within the range of the normal subjects than in the nine subjects with elevated fasting insulin concentrations (61 +/- 3 vs. 45 +/- 6%, P less than 0.05). During the hyperglycemic clamp, the insulin secretion rate increased to an average maximum of 6.2-fold over baseline in the normal subjects and 5.8-fold in the obese subjects. Over the same time, the peripheral insulin concentration increased 14.1-fold over baseline in the normals and 16.6-fold over baseline in the obese, indicating a reduction in the clearance of endogenously secreted insulin. Although the fall in insulin clearance tended to be greater in the obese subjects, the differences between the two groups were not statistically significant. Thus, under basal, fasting conditions and during ingestion of a mixed diet, the hyperinsulinemia of obesity results predominantly from increased insulin secretion. In patients with more marked basal hyperinsulinemia and during intense stimulation of insulin secretion, a reduction in insulin clearance may contribute to the greater increase in peripheral insulin concentrations that are characteristic of the obese state.+

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  • The first stage of diabetes development is a long compensatory period when insulin resistance is present and accompanied by increased rates of insulin secretion and increased β-cell mass.

    “The first stage of diabetes development is a long compensatory period when insulin resistance is present and accompanied by increased rates of insulin secretion44 and an increased β-cell mass.39”

    From Prediabetes: a high-risk state for diabetes development (2012) · cites this paper as [44]

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Authors
Polonsky, K. S., Given, B. D., Hirsch, L., Shapiro, E. T., Tillil, H., Beebe, C., Galloway, J. A., Frank, B. H., Karrison, T., & Van Cauter, E.
Affiliations
  • University of Chicago (US)
  • Université Libre de Bruxelles (BE)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1988-02-01
Volume
81
Issue
2
Pages
435-441
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci113338
PMC
PMC329588
OpenAlex
W2132705610
Cited by
444
References
27
Citations by year
2026: 3 · 2025: 5 · 2024: 1 · 2023: 9 · 2022: 18 · 2021: 17 · 2020: 9 · 2019: 12 · 2018: 14 · 2017: 24 · 2016: 19 · 2015: 24 · 2014: 13 · 2013: 21 · 2012: 20
FWCI
9.68
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Eli Lilly and Company
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-31842, DK 20595)
  • National Center for Research Resources (RR-00055)
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 secretion, insulin clearance, hepatic insulin extraction, obesity, hyperinsulinemia, C-peptide, body mass index, hyperglycemic clamp, fasting insulin, mixed diet, insulin secretion rate, endogenous insulin secretion, type 2 diabetes risk, insulin sensitivity index
MeSH terms
Insulin Secretion, Blood Glucose, C-Peptide, Humans, Hyperglycemia, Insulin, Liver, Metabolic Clearance Rate, Obesity

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