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Am J Physiol Endocrinol Metab 281: E966-E974, 2001;
0193-1849/01 $5.00
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Vol. 281, Issue 5, E966-E974, November 2001

Insulin and C-peptide secretion and kinetics in humans: direct and model-based measurements during OGTT

Andrea Tura1, Bernhard Ludvik2, John J. Nolan3, Giovanni Pacini1, and Karl Thomaseth1

1 Institute of Systems Science and Biomedical Engineering, Italian National Research Council, 35127 Padua, Italy; 2 Division of Endocrinology and Metabolism, Department of Medicine 3, University of Vienna Medical School, A-1090 Vienna, Austria; and 3 Department of Endocrinology, St. James's Hospital, Trinity College, Dublin 8, Ireland

To directly evaluate prehepatic secretion of pancreatic hormones during a 3-h oral glucose tolerance test (OGTT), we measured insulin and C-peptide in six healthy control, six obese, and six type 2 diabetic subjects in the femoral artery and hepatic vein by means of the hepatic catheterization technique. Hypersecretion in obesity was confirmed (309 ± 66 nmol in obese vs. 117 ± 22 in control and 79 ± 13 in diabetic subjects, P <=  0.01), whereas early phase secretion was impaired in diabetes. We also measured hepatic insulin extraction (higher in diabetic than in control subjects, P = 0.03) and insulin clearance. The measured data were also used to validate a previously proposed mathematical model, developed to quantify prehepatic secretion, hepatic insulin extraction, and insulin clearance during OGTT, when C-peptide and insulin concentrations are systemically measured. We found good correspondence between experimental data and model estimates for prehepatic insulin secretion (P > 0.3, r2 = 0.93), whereas estimation of hepatic insulin extraction and insulin clearance needs further investigation for improvement.

oral glucose tolerance test; insulin clearance; pancreatic hormones; hepatic catheterization; mathematical modeling


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