title: Reappraisal of the intravenous glucose tolerance index for a simple assessment of insulin sensitivity in mice.
abstract: Mice are increasingly used in studies where measuring insulin sensitivity (IS) is a common procedure. The glucose clamp is labor intensive, cannot be used in large numbers of animals, cannot be repeated in the same mouse, and has been questioned as a valid tool for IS in mice; thus, the minimal model with 50-min intravenous glucose tolerance test (IVGTT) data was adapted for studies in mice. However, specific software and particular ability was needed. The aim of this study was to establish a simple procedure for evaluating IS during IVGTT in mice (CS(I)). IVGTTs (n = 520) were performed in NMRI and C57BL/6J mice (20-25g). After glucose injection (1 g/kg), seven samples were collected for 50 min for glucose and insulin measurements, analyzed with a minimal model that provided the validated reference IS (S(I)). By using the regression CS(I) = alpha(1) + alpha(2) x K(G)/AUC(D), where K(G) is intravenous glucose tolerance index and AUC(d) is the dynamic area under the curve, IS was calculated in 134 control animals randomly selected (regression CS(I) vs. S(I): r = 0.66, P < 0.0001) and yielded alpha(1) = 1.93 and alpha(2) = 0.24. K(G) is the slope of log (glucose(5-20)) and AUC(D) is the mean dynamic area under insulin curve in the IVGTT. By keeping fixed alpha(1) and alpha(2), CS(I) was validated in 143 control mice (4.7 +/- 0.2 min*microU(-1)*ml(-1), virtually identical to S(I): 4.7 +/- 0.3, r = 0.89, P < 0.0001); and in 123 mice in different conditions: transgenic, addition of neuropeptides, incretins, and insulin (CS(I): 6.0 +/- 0.4 vs. S(I): 6.1 +/- 0.4, r = 0.94, P < 0.0001). In the other 120 animals, CS(I) revealed its ability to segregate different categories, as does S(I). This easily usable formula for calculating CS(I) overcomes many experimental obstacles and may be a simple alternative to more complex procedures when large numbers of mice or repeated experiments in the same animals are required.
authors.affiliation: Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy. giovanni.pacini@isib.cnr.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Maria
authors.initials: M
authors.lastname: Ahrén
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D019004:Galanin / Q000235:genetics / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D005951:Glucose Tolerance Test / Q000662:veterinary; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology; D019787:Linoleic Acid / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D023421:Models, Animal; D008954:Models, Biological; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C083773:exendin (9-39); D019004:Galanin; D052216:Glucagon-Like Peptide 1; D019787:Linoleic Acid; D005947:Glucose