IVGTT-based simple assessment of glucose tolerance in the Zucker fatty rat: Validation against minimal models

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 (S(I)) and against first- (Φ(1)) and second-phase (Φ(2)) 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 (FPIR(3)-SPIR(3,) t = 3 min and FPIR(5)-SPIR(5), 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 S(I) (Spearman’s correlation coefficient, r = 0.88; P<0.001). Both FPIR(3) and FPIR(5) showed a significant (P<0.001) strong correlation with Φ(1) (r = 0.76 and r = 0.75, respectively). Both SPIR(3) and SPIR(5) showed a significant (P<0.001) strong correlation with Φ(2) (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.