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-cell
function: modeling analysis in normal subjects
1 Consiglio Nazionale delle Ricerche Institute of Systems Science and Biomedical Engineering, 35127 Padua; 2 Department of Internal Medicine and Consiglio Nazionale delle Ricerche Institute of Clinical Physiology, University of Pisa, 56126 Pisa, Italy; and 3 Department of Medicine M (Endocrinology and Diabetes), University Hospital, DK-8000 Aarhus, Denmark
We investigated
-cell function and its relationship to insulin sensitivity in 17 normal volunteers. For insulin secretion (derived by C-peptide
deconvolution), a mathematical model was applied to 24-h triple-meal
tests (MT) as well as oral glucose tolerance tests (OGTT); insulin
sensitivity was assessed by the euglycemic insulin clamp technique. The
-cell model featured a glucose concentration-insulin secretion dose
response (characterized by secretion at 5 mM glucose and slope), a
secretion component proportional to the glucose concentration
derivative, and a time-dependent potentiation factor (modulating the
dose response and accounting for effects of sustained hyperglycemia and
incretins). The -cell dose-response functions estimated from the
whole 24-h MT, the first 2 h of the MT, and the OGTT differed
systematically, because a different potentiation factor was involved.
In fact, potentiation was higher than average during meals (1.6 ± 0.1-fold during the first meal) and had a different time course in the
MT and OGTT. However, if potentiation was accounted for, the 24- and
2-h MT and the OGTT yielded similar dose responses, and most -cell
function parameters were intercorrelated (r = 0.50-0.86, P 
0.05). The potentiation factor was
found to be related to plasma glucose-dependent insulin-releasing
polypeptide concentrations (r = 0.49, P < 0.0001). Among -cell function parameters, only insulin secretion
at 5 mM glucose from MT correlated inversely with insulin sensitivity (24-h MT: r = 
0.74, P < 0.001; 2-h
MT: r = 0.52, P < 0.05), whereas the
dose-response slope and the OGTT parameters did not. In nine other
subjects, reproducibility of model parameters was evaluated from
repeated MTs. Coefficients of variation were generally ~20%, but the
derivative component was less reproducible. We conclude that our model
for the multiple MT yields useful information on -cell function,
particularly with regard to the role of potentiation. With cautious
interpretation, a 2-h MT or a standard OGTT can be used as surrogates
of 24-h tests in assessing spontaneous -cell function.
insulin secretion; glucose-induced insulin release; potentiation of glucose-induced insulin release; insulin sensitivity
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