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Am J Physiol Regul Integr Comp Physiol 297: R1195-R1201, 2009. First published August 26, 2009; doi:10.1152/ajpregu.90851.2008
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Articles

Evaluation of different methods for assessment of insulin sensitivity in Göttingen minipigs: introduction of a new, simpler method

Berit Christoffersen,1 Ulla Ribel,2 Kirsten Raun,1 Valeria Golozoubova,1 and Giovanni Pacini3

1GLP-1 and Obesity Pharmacology and 2Insulin Pharmacology, Novo Nordisk A/S, Måløv, Denmark; and 3Metabolic Unit, Institute of Biomedical Engineering, Consiglio Nazionale delle Ricerche, Padua, Italy

Submitted October 21, 2008 ; accepted in final form August 19, 2009

The use of animal models in diabetes research requires reliable tests for evaluation of insulin sensitivity and β-cell function. Minipigs are being increasingly used in metabolic research, and the aim of this study was to compare different tests and indexes for evaluation of insulin sensitivity and β-cell function in Göttingen minipigs. Hyperinsulinemic, isoglycemic clamp, intravenous (IVGTT) and oral glucose tolerance tests (OGTT), and a modified insulin tolerance test were performed in minipigs fed either low- or high-energy diet. Furthermore, the reproducibility of IVGTT-derived parameters was assessed. Previously described insulin sensitivity indexes [steady-state glucose infusion rate/glucose concentration/insulin concentration from clamp (M/G/I); oral glucose insulin sensitivity (OGIS) and ISIcomp from OGTT; SI from minimal model analysis of IVGTT; and quantitative insulin sensitivity check index from fasting values] were calculated together with an insulin sensitivity index from the modified insulin tolerance test (ISIITT) and a new simple index (S2) derived from the first 30 min of the IVGTT. β-Cell function was assessed from the IVGTT and the OGTT. Reproducibility of the IVGTT-derived parameters was calculated as median intraindividual coefficient of variation (CV%).M/G/I correlated significantly only with S2 (P < 0.05, r = 0.54). S2 furthermore correlated with SI (P < 0.001, r = 0.81), ISIITT (P < 0.001, r = 0.57), and the two indexes from OGTT, ISIcomp (P < 0.001, r = 0.78) and OGIS (p < 0.05, r = 0.48). No correlation was found between β-cell function indexes from OGTT and IVGTT. The median CV% of the new S2 index was 13. In conclusion, the new simple index of insulin sensitivity, S2, was revealed to be useful for evaluation of insulin sensitivity in pigs.

glucose tolerance; β-cell function; intravenous glucose tolerance test; oral glucose tolerance test; clamp



Address for reprint requests and other correspondence: B. Christoffersen, GLP-1 and Obesity Pharmacology, Novo Nordisk Park F6.1.30, DK-2760 Måløv, Denmark (e-mail: BQC{at}novonordisk.com).







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