They are feasible. Calum Sutherland developed a model which they reported on a few years ago. Here is the link to their paper.

http://www.sciencedirect.com/science/article/pii/S0006295210004454

Hope this helps.

Thank you so much Craig. This is indeed a great help. Do you have any idea about kinases as markers?

One potential problem of using kinases as biomarkers is that their activity rather than their expression levels are often much more relevant to mechanisms of disease. Perhaps, if you can narrow down some candidate kinases, such as JNK in the case of diabetes, you can perform studies to assess whether there is a linear relationship between expression levels and kinase activity. Alternatively, you could use activation state-specific antibodies to assess the validity of a kinase as a biomarker.

Craig Beall's response here is great - the paper from Calum Sutherland's lab is a great example of a cell line model of insulin resistance.

However as far as kinases as biomarkers of diabetes - I'd be very wary. The reason being that the activity of PKB for instance is so tightly coupled to glucose uptake that only 30% max activity is required to saturate GLUT4 translocation and only about 10% of PI3K activity is required for max PKB activity. As a result if you have in intervention that causes an apparent reduction in PKB activity it may not actually be physiologicaly relevant to the outcome measure of something like glucose uptake. In my book the best measure will still be insulin stimulated glucose uptake - or in the case of Calum Sutherland's model the ability of insulin to repress gluconeogenic gene expression in liver cells.

There are some other measures that could give you a read out of an insulin resistant state like what @Jonathon Winnay suggests with JNK etc and indeed always look to measure the activity or a good surragote of activity as opposed to just expression.

Finally serine phosphorylation of IRS1/2 may additionally be indicators of an insulin resistant state - the best measure would be a change in insulin stimulated IRS1/2 associated PI3K activity or p85 assocaition with a co-IP. Personally I would always look to measure the response of the system to a stimulus such as insulin. Often baseline measures are not that informative.

Hope this helps,

Lee.

Thank you David. This will help. Will get back to you soon.