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INNOVATIVE METHODOLOGY

ENDOCRINE PHYSIOLOGY AND METABOLISM

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

¹Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy; and ²Department of Clinical Sciences, Division of Medicine, Lund University, Lund, Sweden

Submitted 7 July 2008 ; accepted in final form 4 February 2009

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 = ₁ + 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 ₁ = 1.93 and 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 ₁ and ₂, CS_I was validated in 143 control mice (4.7 ± 0.2 min·µU^–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.

insulin resistance; glucose effectiveness; animal model; pituitary adenylate cyclase-activating polypeptide; glucagon-like peptide-1; intravenous glucose tolerance test

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