Evaluation of different methods for assessment of insulin sensitivity in Gottingen minipigs: introduction of a new, simpler method.
The use of animal models in diabetes research requires reliable tests for evaluation of insulin sensitivity and beta-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 beta-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 ISI(comp) from OGTT; S(I) 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 (ISI(ITT)) and a new simple index (S2) derived from the first 30 min of the IVGTT. beta-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 S(I) (P < 0.001, r = 0.81), ISI(ITT) (P < 0.001, r = 0.57), and the two indexes from OGTT, ISI(comp) (P < 0.001, r = 0.78) and OGIS (p < 0.05, r = 0.48). No correlation was found between beta-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.
Christoffersen
Berit
B
GLP-1 and Obesity Pharmacology, Novo Nordisk A/S, Måløv, Denmark. BQC@novonordisk.com
Ribel
Ulla
U
Raun
Kirsten
K
Golozoubova
Valeria
V
Pacini
Giovanni
G
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D044882:Glucose Metabolism Disorders / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D015203:Reproducibility of Results; D013004:Somatostatin / Q000008:administration & dosage; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D005947:Glucose