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Am J Physiol Regul Integr Comp Physiol (February 11, 2009). doi:10.1152/ajpregu.90575.2008
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Submitted on July 7, 2008
Revised on February 4, 2009
Accepted on February 4, 2009

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

Giovanni Pacini1*, Maria Ahren2, and Bo Ahren2

1 Institute of Biomedical Engineering
2 Lund University

* To whom correspondence should be addressed. E-mail: Giovanni.Pacini{at}isib.cnr.it.

Mice are increasingly used in studies where measuring insulin sensitivity (IS) is a common procedure. 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 50min-intravenous glucose (IVGTT) data was adapted in mice. However, specific software and particular ability is needed. Aim of this study was to establish a simple procedure for evaluating IS during IVGTT in mice (CSI). IVGTT (n=520) were performed in NMRI and C57BL/6J mice (20-25g). After glucose injection (1 g/kg), 7 samples were collected until 50 min for glucose and insulin measurements, analyzed with minimal model which provided the validated reference IS (SI). By using the regression CSI={alpha}1+{alpha}2xKG/AUCD, IS was calculated in 134 control animals randomly selected (regression CSI vs. SI: r=0.66, p<0.0001) and yielded {alpha}1=1.93 and {alpha}2=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 {alpha}1 and {alpha}2, CSI was validated in 143 control mice (4.7±0.2 min-1µU-1ml, 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, insulin (CSI: 6.0±0.4 vs. SI: 6.1±0.4, r=0.94, p<0.0001). In other 120 animals, CSI revealed its ability to segregate different categories, as SI does. 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.




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B. Christoffersen, U. Ribel, K. Raun, V. Golozoubova, and G. Pacini
Evaluation of different methods for assessment of insulin sensitivity in Gottingen minipigs: introduction of a new, simpler method
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2009; 297(4): R1195 - R1201.
[Abstract] [Full Text] [PDF]




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