Effect of a variable hepatic insulin clearance on the postprandial insulin profile: insights from a model simulation study

A Caumo, I Florea, L Luzi - Acta diabetologica, 2007 - Springer
A Caumo, I Florea, L Luzi
Acta diabetologica, 2007Springer
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 …
Abstract
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.
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