A minimal model of insulin secretion and kinetics to assess hepatic insulin extraction

Abstract

The liver is the principal site of insulin degradation, and assessing its ability to extract insulin is important to understand several pathological states. Noninvasive quantification of hepatic extraction (HE) in an individual requires comparing the profiles of insulin secretion (ISR) and posthepatic insulin delivery rate (IDR). To do this, we propose here the combined use of the classical C-peptide minimal model with a new minimal model of insulin delivery and kinetics. The models were identified on insulin-modified intravenous glucose tolerance test (IM-IVGTT) data of 20 healthy subjects. C-peptide kinetics were fixed to standard population values, whereas insulin kinetics were assessed in each individual, along with IDR parameters, thanks to the presence of insulin decay data observed after exogenous insulin administration. From the two models, profiles of ISR and IDR were predicted, and ISR and IDR indexes of beta-cell responsivity to glucose in the basal state, as well as during first- and second-phase secretion, were estimated. HE profile, obtained by comparing ISR and IDR profiles, showed a rapid suppression immediately after the glucose administration. HE indexes, obtained by comparing ISR and IDR indexes, indicated that the liver is able to extract 70 +/- 9% of insulin passing through it in the basal state and 54 +/- 14% during IM-IVGTT. In conclusion, insulin secretion, kinetics, and hepatic extraction can be reliably assessed during an IM-IVGTT by using insulin and C-peptide minimal models.