Effect of a variable hepatic insulin clearance on the postprandial insulin profile: insights from a model simulation study.
The liver plays a pivotal role in determining postprandial insulin levels because it is responsible for the extraction of a large (approximately 50%) fraction of the newly secreted insulin by the pancreas. Evidence exists that hepatic insulin extraction is not constant during a meal, but is inhibited because of saturable receptor-mediated mechanisms and/or increase in hepatic blood flow. The aim of the present study was to exploit the ability of mathematical model simulation to shed light on the role of a variable hepatic insulin extraction during a meal. Mathematical models of insulin secretion and kinetics were coupled to provide predictions for the concentration of insulin in plasma following a meal under the assumptions of either a constant or a time-varying hepatic insulin clearance. Our results indicate that a 20% inhibition in hepatic clearance is able to remarkably enhance the plasma insulin level following a meal. These results emphasise the need for simple and accurate methods to measure the time course of hepatic insulin extraction under nonsteady-state conditions.
Caumo
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Unit of Nutrition and Metabolism, Department of Medicine, San Raffaele Scientific Institute, Via Olgettina 60, I-20132, Milan, Italy.
Florea
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Luzi
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D001786:Blood Glucose / Q000032:analysis; D003198:Computer Simulation; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D008962:Models, Theoretical; D019518:Postprandial Period
D001786:Blood Glucose; D007328:Insulin