We are running hyperinsulinemic euglycemic clamp in mice. But I have always been thinking about what does euglycemia means. Should the fasting glucose value of each individual mouse be the guide for the blood glucose you want to achieve at steady state or should you decide beforehand that every mouse should achieve the same blood glucose values at steady state of the clamp. If a group of mice have lower fasting glucose value than another group, then this first group might need lower GIR to maintain their “own” euglycemic value, but if you would have clamped all mice at the same blood glucose values the group with lower fasting glucose values will probably have a higher GIR. How do you usually do in mouse experiments using the glucose clamp technique?
Since the general consensus would be higher GIR indicating higher insulin sensitivity, which indirectly reflects lower fasting glucose levels, your "second" way of thinking would be more appropriate.
So, the general clamp setup would be choosing a target "mean" blood glucose value (typically 120-150mg/dL, depending on the strain of mice used) for all the mice, so that you could categorize those having lower "mean" GIR as higher insulin resistant and higher "mean" GIR as having lower insulin resistance.
The complete methodology (as pioneered by David Wasserman from Vanderbilt Univ) can be found here: Article Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
orArticle Considerations in the Design of Hyperinsulinemic-Euglycemic ...
If comparisons are made based on their individual fasting blood glucose levels, the noise in the cumulative data will be almost impossible to draw conclusions. Because each mouse will be a categorical data point by itself.
The hyperinsulinemic-euglycemic is gold-standard" in assessing insulin sensitivity ,it is widely used in clinics and laboratories to measure insulin action on glucose utilization in humans and animals for clinical and basic science research ,
References
1. Li Kang, .Hyperinsulinemic-euglycemic Clamp. Mouse Metabolic Phenotyping Centers; Vanderbilt University;2014
2. Hughey CC, Hittel DS, Johnsen VL, Shearer J. Hyperinsulinemic-Euglycemic Clamp in the Conscious Rat. Journal of Visualized Experiments : JoVE. 2011;(48):2432. doi:10.3791/2432.
3. Kim JK.Hyperinsulinemic-euglycemic clamp to assess insulin sensitivity in vivo. Methods Mol Biol. 2009;560:221-38. doi: 10.1007/978-1-59745-448-3_15.
Louise, what you are thinking is absolutely right. Clamping blood glucose levels from two different mouse phenotypes should be resulted in different GIR, if there is different insulin sensitivity between groups. Euglycemia should be determined baseline blood glucose level before infusing insulin. If one group of mice show120mg/dL and another group of mice show 150mg/dL, either 120, 150, or around 130 should be okay. Bottom line is you should "clamp" blood glucose levels to the same range give or take 130-140. As Adithya suggested above, Vanderbilt University have invented this technique in mouse and published wonderful method articles and research articles. They also offer annual clamp class; https://labnodes.vanderbilt.edu/mmpc. Ask advice or question to them. Good luck!
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