C-Peptide-based assessment of insulin secretion in the Zucker Fatty rat: a modelistic study.

ABSTRACT: A C-peptide-based assessment of ?-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT) was performed in seven Zucker fatty rats (ZFR), 7-to-9 week-old, and seven age-matched Zucker lean rats (ZLR). The minimal model of C-peptide (CPMM), originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM). Our results showed that the present CPMM-based interpretation of data is able to: 1) provide a suitable fit of C-Peptide data; 2) achieve a satisfactory estimation of parameters of interest 3) quantify both insulin secretion by estimating the time course of pre-hepatic secretion rate, SR(t), and total insulin secretion, TIS, and pancreatic sensitivity by means of three specific indexes of ?-cell responsiveness to glucose stimulus (first-phase, ?(1), second-phase, ?(2), and steady-state, ?(ss), never assessed in Zucker rats before; 4) detect the significant enhancement of insulin secretion in the ZFR, in face of a severe insulin-resistant state, previously observed only using a purely experimental approach. Thus, the methodology presented here represents a reliable tool to assess ?-cell function in the Zucker rat, and opens new possibilities for the quantification of further processes involved in glucose homeostasis such as the hepatic insulin degradation.

SUBMITTER: Di Nardo F 

PROVIDER: S-EPMC4418729 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature