题名：Minimal modeling of insulin secretion in the perfused rat pancreas: a drug effect case study.
作者：RIZ M; PEDERSEN MG; TOFFOLO GM; HASCHKE G; SCHNEIDER HC; KLABUNDE T; MARGERIE D; COBELLI C;
来源：Am J Physiol Endocrinol Metab. 2014 Jan 14. [ IF= 0.00 ] ]
摘要：The experimental protocol of the perfused rat pancreas is commonly used to
evaluate beta-cell function. In this context mathematical models become useful
tools through the determination of indexes that allow the assessment of beta-cell
function in different experimental groups, and the quantification of the effects
of anti-diabetic drugs, secretagogues, or treatments. However, a minimal model
applicable to the isolated perfused rat pancreas was unavailable so far. In this
work, we adapt the C-peptide minimal model, previously applied to the intravenous
glucose tolerance test, to obtain a specific model for the experimental settings
of the perfused pancreas. Using the model, it is possible to estimate indexes
describing beta-cell responsivity for first (PhiD) and second phase (PhiS, T) of
insulin secretion. The model was initially applied to untreated pancreata, and
afterwards used for the assessment of pharmacologically relevant agents (the gut
hormone GLP1, the potent GLP1-receptor agonist, lixisenatide, and a GPR40/FFAR1
agonist, SAR1), to quantify and differentiate their effect on insulin secretion.
Model fit was satisfactory and parameters were estimated with good precision for
both untreated and treated pancreata. Model application showed that lixisenatide
reaches improvement of beta-cell function similar to GLP1 (11.7 vs 13.1 fold
increase in PhiD and 2.3 vs 2.8 fold increase in PhiS) and demonstrated that SAR1
leads to an additional improvement of beta-cell function even in the presence of
postprandial GLP1 levels.