Open AccessC-Peptide-Based Assessment of Insulin Secretion in the Zucker Fatty Rat: A Modelistic Study
Author(s) -
Francesco Di Nardo,
Carla Cogo,
Emanuela Faelli,
Micaela Morettini,
Laura Burattini,
Piero Ruggeri
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0125252
Subject(s) - medicine , endocrinology , insulin , glucose homeostasis , c peptide , secretion , glucose tolerance test , diabetes mellitus , biology , insulin resistance
A C-peptide-based assessment of β-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-9week-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 β-cell responsiveness to glucose stimulus (first-phase, Ф 1 , second-phase, Ф 2 , and steady-state, Ф 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 β-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.