Quantitative indexes of β-cell function during graded up&down glucose infusion from C-peptide minimal models
Abstract
Availability of quantitative indexes of insulin secretion is important for definition of the alterations in β-cell responsivity to glucose associated with different physiopathological states. This is presently possible by using the intravenous glucose tolerance test (IVGTT) in conjunction with the C-peptide minimal model. However, the secretory response to a more physiological slowly increasing/decreasing glucose stimulus may uncover novel features of β-cell function. Therefore, plasma C-peptide and glucose data from a graded glucose infusion protocol (seven 40-min periods of 0, 4, 8, 16, 8, 4, and 0 mg · kg−1 · min−1) in eight normal subjects were analyzed by use of a new model of insulin secretion and kinetics. The model assumes a two-compartment description of C-peptide kinetics and describes the stimulatory effect on insulin secretion of both glucose concentration and the rate at which glucose increases. It provides in each individual the insulin secretion profile and three indexes of pancreatic sensitivity to glucose: Φ s, Φ d, and Φ b, related, respectively, to the control of insulin secretion by the glucose level (static control), the rate at which glucose increases (dynamic control), and basal glucose. Indexes (means ± SE) were Φ s = 18.8 ± 1.8 (10 9 min−1), Φ d = 222 ± 30 (10 9), and Φ b = 5.2 ± 0.4 (10 9 min−1). The model also allows one to quantify the β-cell times of response to increasing and decreasing glucose stimulus, equal to 5.7 ± 2.2 (min) and 17.8 ± 2.0 (min), respectively. In conclusion, the graded glucose infusion protocol, interpreted with a minimal model of C-peptide secretion and kinetics, provides a quantitative assessment of pancreatic function in an individual. Its application to various physiopathological states should provide novel insights into the role of insulin secretion in the development of glucose intolerance.
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The model describing glucose-dependent insulin secretion is linear in both Φd and Φs; doubling Φd or Φs results in doubling SRd or SRs, respectively.
“the model describing the glucose-dependent insulin secretion (4, 28) is linear in both Φd and Φs; i.e., doubling Φd or Φs results in doubling SRd or SRs, respectively.”
From A model of GLP-1 action on insulin secretion in nondiabetic subjects (2010) · cites this paper as [28]
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- Authors
- Toffolo, G., Breda, E., Cavaghan, M. K., Ehrmann, D. A., Polonsky, K. S., & Cobelli, C.
- Affiliations
- University of Padua (IT)
- University of Chicago (US)
- Washington University in St. Louis (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2001-01-01
- Volume
- 280
- Issue
- 1
- Pages
- E2-E10
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2162028789
- Cited by
- 112
- References
- 20
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 9 · 2012: 3
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1k23dk002742-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-31842, DK 20595, DK-02742)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- beta-cell function, insulin secretion, C-peptide kinetics, two-compartment model, impaired glucose tolerance, intravenous glucose tolerance test
- MeSH terms
- Insulin Secretion, Adult, B-Lymphocytes, Blood Glucose, C-Peptide, Female, Glucose Tolerance Test, Humans, Insulin, Male, Models, Biological
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