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.