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1 Department of Information Engineering, University of Padova, Padova, Italy
2 Department of Internal Medicine, Division of Endocrinology, Diabetes, Metabolism & Nutrition, Mayo Clinic & Foundation, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: cobelli{at}dei.unipd.it.
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 post-hepatic delivery (IDR). To do this, we propose here the combined use of the classic 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, while insulin kinetics were assessed in each individual along with IDR parameters thanks to the presence of insulin decay data observed after the exogenous insulin administration. From the two models, profiles of ISR and IDR were predicted and ISR and IDR indices 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 indices, obtained by comparing ISR and IDR indices, indicated that the liver is able to extracts 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.
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