A model for glucose control of insulin secretion during 24 h of free living.
The aim of this work was to develop a mathematical model describing the functional dependence of insulin secretion on plasma glucose concentrations during 24 h of free living. We obtained hourly central venous blood samples from a group of healthy volunteers who spent 24 h in a calorimetric chamber, where they consumed standardized meals. Insulin secretory rates were reconstructed from plasma C-peptide concentrations by deconvolution. The relationship between insulin release and plasma glucose concentrations was modeled as the sum of three components: a static component (describing the dependence on plasma glucose concentration itself, with an embedded circadian oscillation), a dynamic component (modeling the dependence on glucose rate of change), and a residual component (including the fraction of insulin secretion not explained by glucose levels). The model fit of the individual 24-h secretion profiles was satisfactory (within the assigned experimental error of glucose and C-peptide concentrations). The static component yielded a dose-response function in which insulin release increased quasi-linearly (from 40 to 400 pmol/min on average) over the range of 4-9 mmol/l glucose. The dynamic component was significantly different from zero in coincidence with meal-related glucose excursions. The circadian oscillation and the residual component accounted for the day/night difference in the ability of glucose to stimulate insulin release. Over 24 h, total insulin release averaged 257+/-58 nmol (or 43+/-10 U). The static and dynamic component together accounted for approximately 80% of total insulin release. The model proposed here provides a detailed robust description of glucose-related insulin release during free-living conditions. In nondiabetic subjects, non-glucose-dependent insulin release is a small fraction of total insulin secretion.
Metabolism Unit of the Consiglio Nazionale delle Recherche, Institute of Clinical Physiology, University of Pisa, Italy.
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Mari
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Camastra
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Toschi
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Giancaterini
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Gastaldelli
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Mingrone
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Ferrannini
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008962:Models, Theoretical
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin