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

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 (SI). By using the regression CSI = α1 + α2 × KG/AUCD, where KG is intravenous glucose tolerance index and AUCd is the dynamic area under the curve, IS was calculated in 134 control animals randomly selected (regression CSI vs. SI: r = 0.66, P < 0.0001) and yielded α1 = 1.93 and α2 = 0.24. KG is the slope of log (glucose5-20) and AUCD is the mean dynamic area under insulin curve in the IVGTT. By keeping fixed α1 and α2, CSI was validated in 143 control mice (4.7 ± 0.2 min·μU−1·ml−1, virtually identical to SI: 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 SI. 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.