Excellent paper!!! I was thinking just as I was reading it that in the case of diabetes you might find a similar example where the environment has a mayor influence in the insensitivity to insulin. Yet in some trials (I could find the papers if you can not) have managed to only to treat but to cure diabetics by a (extremely) low carbohydrate diet, something like 600 cal/day. In other words we did not evolve to have continuous high carbohydrate intake = constitutive stimulation of sugar pathways. You could try the same in this case and might find a very good example. Also the same apply to receptors which are constitutively active, in the absence of ligand, yet, despite their very low activity, they can cause tumours or other problems.

Excellent paper!!! I was thinking just as I was reading it that in the case of diabetes you might find a similar example where the environment has a mayor influence in the insensitivity to insulin. Yet in some trials (I could find the papers if you can not) have managed to only to treat but to cure diabetics by a (extremely) low carbohydrate diet, something like 600 cal/day. In other words we did not evolve to have continuous high carbohydrate intake = constitutive stimulation of sugar pathways. You could try the same in this case and might find a very good example. Also the same apply to receptors which are constitutively active, in the absence of ligand, yet, despite their very low activity, they can cause tumours or other problems.

This is really interesting. Actually I am no epxert in Diabetes but we did a lot of research in Dresden University (Group of Professor Solimena).

Do you mean that by reducing the diet you can "disrupt" such a feedback in DM?

Very interesting your article, but my lab's specialty is in structural bioinformatics.

Here you can find the article about reversing diabetes by an extra-low-carbohydrate diet:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168743/

I guess that the lack of continuous stimulation (feedback) in the diet group results in changes in sensitivity to insulin. In DMII big part of the problem might be the lack, or very low, response to insulin and that might be due to a high carbohydrate-driven feedback that keep the b-cells in a non-responsive mode.

We have recently published collaborative paper where our computational predictions of TET2 (an epigenetic regulator) interactors have been confirmed in vitro. That is the first paper explaining the mechanism of TET2 wt inactivation in chronic myeloid leukemia http://onlinelibrary.wiley.com/doi/10.1002/jcb.24154/abstract

I am also attaching the paper describing bioinformatics approach applied. In case of your study, I would suggest analyzing feedback loops proteins and identifying (if possible) their common spectral characteristics. After that, I believe that you would be capable of identifying proteins with loop-specific spectral characteristics from human proteome sequences.