Reappraisal of the intravenous glucose tolerance index for a simple assessment of insulin sensitivity in mice

Pacini G, Ahren M, Ahren B. Reappraisal of the intravenous glucose tolerance index for a simple assessment of insulin sensitivity in mice. Am J Physiol Regul Integr Comp Physiol 296: R1316-R1324, 2009. First published February 11, 2009; doi: 10.1152/ajpregu.90575.2008.- 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 (CSI). 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-perpendicular to). By using the regression CS perpendicular to = 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 CSI vs. S-I: r = 0.66, P < 0.0001) and yielded alpha(1) = 1.93 and alpha(2) = 0.24. KG is the slope of log (glucose(5-20)) and AUCD is the mean dynamic area under insulin curve in the IVGTT. By keeping fixed alpha(1) and alpha(2), CSI was validated in 143 control mice (4.7 +/- 0.2 min . mu U- . 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 (CSI: 6.0 +/- 0.4 vs. SI: 6.1 +/- 0.4, r = 0.94, P < 0.0001). In the other 120 animals, CSI revealed its ability to segregate different categories, as does S-I. This easily usable formula for calculating CSI 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.