IPK ja OFF-signal - systeemi ( vesiliukoista tietä) insuliinisignalointiin

Inositol phosphate kinase, a newly found (2010) signal system for Insulin.

http://physiologyonline.physiology.org/content/20/4/271

Our metabolic balance is dependent upon acute and transient responses to insulin.   One common way to achieve good control of many metabolic systems is so-called feedback regulation.  That is, correct metabolic activity is often the result of a balance between an "off" and an "on" reaction or control system.  Is this also found for insulin signaling?
In a recent paper in Cell 143, 897-910 2010, Chakraborty et. al. report a new player in the insulin story.  This is reviewed in the same issue of Cell by Brendan D. Manning Cell 143 861-862 2010 (DOI 10.1016/j.cell.2010.11.040).  They have discovered an insulin receptor product which has not been reported earlier.  Activation of the insulin receptor stimulates both phosphorylation of IRS1 and activation of inositol hexakisphosphate (IP6) kinase (IP6K1).  The latter yields 5-diphospho-inositolpentakisphosphate (5-PP-IP5 or IP7).  IP7 binds to Akt, inactivating it and preventing its function as a substrate for mTORC2* and PDK1 phosphorylation.  That is, insulin produces signal substances that both activate and deactivate Akt.  The "on" signal is the PIP2-PIP3 sequence.  The "off" signal is the IP6-IP7 sequence.  The balance between these may dominate insulin regulation of metabolism.  Perhaps even more important is the possibility that the key to understanding "insulin resistance" may lie in the balance between these. 



*mTOR
mTOR is a nuclear serine/threonine protein kinase found in two complexes (mTORC1 and mTORC2) in most of the body's tissues.  These appear to be essential in the regulation of metabolism, including organization of the insulin and growth factor signals.  mTOR is also an important element in the ageing process and in development of several types of cancer.  There is a very large literature concerning mTOR.  An analysis of this lies beyond the scope of Medbio.info.  However, I acknowledge that mTOR is of major interest for further developments in medicine.  I will advise those who are interested to download two important articles from Wikipedia.  1: http://en.wikipedia.org/wiki/MTOR.  2: http://en.wikipedia.org/wiki/Discovery_and_development_of_mTOR_inhibitors.