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Kidney Failure SymptomsSubject: What Fatty Acids We Eat
Author: ironjustice@aol.comDate: 27 Sep 2008
Discovery offers new understanding of diabetes drug target
September 26, 2008
Team from University of Leicester reveal how the protein PPAR gamma
binds to 8 fatty acids
Scientists at the University of Leicester have published findings
about a new advance in the study of major diabetes drug target.
The advance - described by the researchers as 'very significant' -
could lead to new drugs being developed to target a protein that plays
a critical role in controlling the way the body breaks down sugar.
Professor John Schwabe and his team from the University of Leicester
Department of Biochemistry (together with teams from Japan and
Hungary) have been studying the protein, PPAR gamma. PPAR gamma is a
major drug target for the treatment of type 2 diabetes. Although it
was known how drugs are able to activate this protein, until this
study, using the sophisticated technique of X-ray Crystallography, it
was not clear how PPAR gamma is naturally activated in the body.
X-ray Crystallography is the principal method by which the detailed 3-
dimensional structures of molecules - especially the molecules of
living systems - have been discovered. It is achieved by firing X-rays
at the target and creating its structures by analysing how the x-rays
scatter into many different directions.
Through this method, the Leicester team have shown how PPAR gamma
binds to eight different fatty acids, derived in part from what we
eat. They found that many of these acids joined irreversibly with the
protein and led to its long term activation. They have also shown that
sometimes two fatty acids bind simultaneously, which might mean that
PPAR gamma could be targeted by a mixture of drugs.
Professor John Schwabe, who led the Leicester project with his team,
including Dr Toshimasa Itoh and Dr Louise Fairall, said: "The finding
that natural activators for PPAR gamma couple irreversibly to the PPAR
gamma receptor dramatically changes our understanding of how this
receptor is activated.
"It may also allow for the design of novel pharmaceuticals that give
longer term activation of PPAR gamma, at lower doses, without some of
the side effects of the current generation of drugs."
Professor Schwabe said: "PPAR gamma is a critical player in the
increasingly prevalent metabolic disease of type 2 diabetes which
affects more than 180 million people worldwide (World Health
Organisisation) and in the UK alone costs the NHS £9.6 million every
day.
"PPARgamma is activated by two widely prescribed anti-diabetic
insulin- sensitising drugs, Actos and Avandia. However the identity of
the natural activators for PPAR gamma has remained unclear.
"Our breakthrough is important because it reveals for the first time
that how this protein is activated by naturally-occuring fatty acids.
This knowledge will help in the design of future novel pharmaceutical
agents."
University of Leicester
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