title: Assessment of hepatic insulin degradation, in normoglycemic hypertensive patients, by minimal modelling of standard intravenous glucose tolerance test data.
abstract: Role of hepatic insulin degradation in modulating insulin delivery to peripheral circulation, in insulin-resistant hypertensive patients, is not yet fully understood. This issue was investigated here by a novel application to hypertension of a previously proposed minimal modelling of insulin and C-peptide data, using population values for insulin and C-peptide kinetics parameters. Data, from frequently sampled intravenous glucose tolerance test (FSIGTT), were analysed in ten normoglycemic, hypertensive patients (H-group), compared with eight normoglycemic, normotensive subjects (N-group), matched for age, gender and body mass index. Minimal modelling of C-peptide and insulin data provided beta-cell responsiveness to glucose perturbation (first, Phi(1), second, Phi(2), and basal, Phi(b), phase), insulin secretion rate, ISR(t) and total pre-hepatic insulin secretion, TIS, as well as insulin delivery rate, IDR(t), and total insulin delivery, TID, into plasma, over 5-h test. Instantaneous normalized hepatic insulin degradation rate was computed as HIDR(t)=1-[IDR(t)/ISR(t)]. In our H-group, insulin sensitivity, S(I), assessed by minimal model of glucose kinetics, showed a 56% reduction, which confirmed deterioration of insulin action in hypertension. This was associated with significant increase in Phi(1) (105%), TIS (55%) and TID (62%). No significant alterations were observed in other characteristic parameters of secretion and hepatic degradation of insulin, such that no significant difference was observed in HIDR(t) between our H and N groups. In conclusion, an increase of first phase and total insulin secretion occurring, in our H-group, in the presence of no alteration of hepatic insulin degradation, resulted in up-regulation of total insulin delivered to plasma (TID) for insulin-resistance compensation.
authors.affiliation: Department of Biomedical, Electronics and Telecommunication Engineering, Polytechnic University of Marche, 60131 Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Nardo
authors.forename: Massimo
authors.initials: M
authors.lastname: Boemi
authors.forename: Roberto
authors.initials: R
authors.lastname: Burattini
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003198:Computer Simulation; D003936:Diagnosis, Computer-Assisted / Q000379:methods; D005260:Female; D005951:Glucose Tolerance Test / Q000379:methods*; D006801:Humans; D006943:Hyperglycemia / Q000175:diagnosis / Q000378:metabolism; D006973:Hypertension / Q000175:diagnosis* / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D001786:Blood Glucose; D007328:Insulin