C-Peptide-based assessment of insulin secretion in the Zucker Fatty rat: a modelistic study.
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-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 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.
Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.
Francesco
F
Di Nardo
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Carla E
CE
Cogo
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Emanuela
E
Faelli
Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy; Presently at Interuniversity Centre of Bioengineering of the Human Neuromusculoskeletal System, University of Rome "Foro Italico", Rome, Italy.
Micaela
M
Morettini
Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.
Laura
L
Burattini
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Piero
P
Ruggeri
D000818:Animals; D001786:Blood Glucose; D002096:C-Peptide / Q000378:metabolism*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D051381:Rats; D011924:Rats, Zucker; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005947:Glucose