title: IVGTT-based simple assessment of glucose tolerance in the Zucker fatty rat: Validation against minimal models.
abstract: For the assessment of glucose tolerance from IVGTT data in Zucker rat, minimal model methodology is reliable but time- and money-consuming. This study aimed to validate for the first time in Zucker rat, simple surrogate indexes of insulin sensitivity and secretion against the glucose-minimal-model insulin sensitivity index (SI) and against first- (Φ1) and second-phase (Φ2) β-cell responsiveness indexes provided by C-peptide minimal model. Validation of the surrogate insulin sensitivity index (ISI) and of two sets of coupled insulin-based indexes for insulin secretion, differing from the cut-off point between phases (FPIR3-SPIR3, t = 3 min and FPIR5-SPIR5, t = 5 min), was carried out in a population of ten Zucker fatty rats (ZFR) and ten Zucker lean rats (ZLR). Considering the whole rat population (ZLR+ZFR), ISI showed a significant strong correlation with SI (Spearman's correlation coefficient, r = 0.88; P<0.001). Both FPIR3 and FPIR5 showed a significant (P<0.001) strong correlation with Φ1 (r = 0.76 and r = 0.75, respectively). Both SPIR3 and SPIR5 showed a significant (P<0.001) strong correlation with Φ2 (r = 0.85 and r = 0.83, respectively). ISI is able to detect (P<0.001) the well-recognized reduction in insulin sensitivity in ZFRs, compared to ZLRs. The insulin-based indexes of insulin secretion are able to detect in ZFRs (P<0.001) the compensatory increase of first- and second-phase secretion, associated to the insulin-resistant state. The ability of the surrogate indexes in describing glucose tolerance in the ZFRs was confirmed by the Disposition Index analysis. The model-based validation performed in the present study supports the utilization of low-cost, insulin-based indexes for the assessment of glucose tolerance in Zucker rat, reliable animal model of human metabolic syndrome.
authors.affiliation: Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Micaela
authors.initials: M
authors.lastname: Morettini
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Faelli
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Perasso
authors.affiliation: Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Fioretti
authors.affiliation: Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Burattini
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggeri
authors.affiliation: Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Francesco
authors.identifier: http://orcid.org/0000-0002-5362-3776
authors.initials: F
authors.lastname: Di Nardo
mesh_terms: D000818:Animals; D015415:Biomarkers; D001786:Blood Glucose; D001835:Body Weight; D004195:Disease Models, Animal; D005215:Fasting; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D051381:Rats; D011924:Rats, Zucker
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D005947:Glucose