Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients.
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We undertook this study to examine the accuracy of plasma C-peptide as a marker of insulin secretion. The peripheral kinetics of biosynthetic human C-peptide (BHCP) were studied in 10 normal volunteers and 7 insulin-dependent diabetic patients. Each subject received intravenous bolus injections of BHCP as well as constant and variable rate infusions. After intravenous bolus injections the metabolic clearance rate of BHCP (3.8 +/- 0.1 ml/kg per min, mean +/- SEM) was not significantly different from the value obtained during its constant intravenous infusion (3.9 +/- 0.1 ml/kg per min). The metabolic clearance rate of C-peptide measured during steady state intravenous infusions was constant over a wide concentration range. During experiments in which BHCP was infused at a variable rate, the peripheral concentration of C-peptide did not change in proportion to the infusion rate. Thus, the infusion rate of BHCP could not be calculated accurately as the product of the C-peptide concentration and metabolic clearance rate. However, the non-steady infusion rate of BHCP could be accurately calculated from peripheral C-peptide concentrations using a two-compartment mathematical model when model parameters were derived from the C-peptide decay curve in each subject. Application of this model to predict constant infusions of C-peptide from peripheral C-peptide concentrations resulted in model generated estimates of the C-peptide infusion rate that were 101.5 +/- 3.4% and 100.4 +/- 2.8% of low and high dose rates, respectively. Estimates of the total quantity of C-peptide infused at a variable rate over 240 min based on the two-compartment model represented 104.6 +/- 2.4% of the amount actually infused. Application of this approach to clinical studies will allow the secretion rate of insulin to be estimated with considerable accuracy. The insulin secretion rate in normal subjects after an overnight fast was 89.1 pmol/min, which corresponds with a basal 24-h secretion of 18.6 U.
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Peripheral insulin concentrations do not represent insulin secretion but rather the sum of pancreatic insulin secretion, hepatic insulin extraction, and distribution into the circulating compartment.
“However, peripheral insulin concentrations do not represent insulin secretion but rather the sum of pancreatic insulin secretion, hepatic insulin extraction, and distribution into the circulating compartment.”
From A model of GLP-1 action on insulin secretion in nondiabetic subjects (2010) · cites this paper as [24]
The Calculations section (page not provided) says insulin and C-peptide are cosecreted, whereas C-peptide is not extracted by the liver. The Discussion (page not provided) shows that peripheral C-peptide concentrations do not directly track secretion under nonsteady-state conditions because of distribution and clearance. These passages support the general warning against equating a peripheral concentration with secretion, but they do not state the claimed three-part account specifically for peripheral insulin concentrations. (LLM, conf=0.80)
Experimental — accuracy not yet measuredC-peptide and insulin are secreted in equimolar fashion and C-peptide is not extracted by the liver.
“given that both are secreted in an equimolar fashion and C-peptide is not extracted by the liver.”
From A model of GLP-1 action on insulin secretion in nondiabetic subjects (2010) · cites this paper as [24]
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- Authors
- Polonsky, K. S., Licinio-Paixao, J., Given, B. D., Pugh, W., Rue, P., Galloway, J., Karrison, T., & Frank, B.
- Affiliations
- University of Chicago (US)
- Eli Lilly (United States) (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1986-01-01
- Volume
- 77
- Issue
- 1
- Pages
- 98-105
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC423314
- OpenAlex
- W1979180498
- Cited by
- 359
- References
- 39
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 1 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 12 · 2015: 14 · 2014: 5 · 2013: 13 · 2012: 7
- FWCI
- 20.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- National Institutes of Health (5r01am031842-03, 5k04am001234-03, AM20595)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- insulin secretion rate, metabolic clearance rate, two-compartment model, C-peptide kinetics, type 1 diabetes, basal insulin secretion, overnight fasting
- MeSH terms
- Insulin Secretion, Adult, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 1, Female, Humans, Infusions, Parenteral, Injections, Intravenous, Insulin, Male, Mathematics, Metabolic Clearance Rate, Models, Biological, Recombinant Proteins
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