PTEN mutation results
in obesity and constitutive insulin sensitivity in human beings.
A team of experts from
the Oxford University discovered the first single gene responsible for
increased sensitivity to the insulin hormone.
condition-insulin resistance which is a common feature of type 2 diabetes
therefore the root cause of insulin sensitivity could provide new opportunities
for following novel cure for diabetes.
PTEN- the tumour-suppressor
phosphatase and tensin homologue has important role in both metabolic signaling
and cellular growth.
The mutations in the
PTEN gene result in increased risk of carcinoma and the biological pathways in
which gene is involved promise better targets for new drugs.
The Oxford University
researchers, along with colleagues at the Babraham Institute in Cambridge, UK,
and the Churchill Hospital in Oxford, UK published their findings in the New
England Journal of Medicine. This research was financially aided by the
Wellcome Trust, the Medical Research Council, the National Institute for Health
Research Oxford Biomedical Research Centre, and the Biotechnology and
Biological Sciences Research Council.
Anna Gloyn of the
Oxford Centre for Diabetes, Endocrinology and Metabolism at the University of
Oxford, the lead author of study said, 'Insulin resistance is a major feature
of type 2 diabetes.
cells in the pancreas may be working hard and pumping out lots of insulin, but
the body's cells no longer respond.'
'Finding a genetic
cause of the opposite -- insulin sensitivity -- gives us a new window on the
biological processes involved. Such understanding could be important in
developing new drugs that restore insulin sensitivity in type 2 diabetes.'
The PTEN gene is known
to encode for an enzyme which is a part of signaling insulin pathway the human
body. PTEN gene also has a role in regulating the body's metabolism. The team
of scientists from the Oxford University was interested in knowing more about
this double role.
Dr Aparna Pal from the
University of Oxford said, 'PTEN is a gene that is heavily involved in
processes for both cell growth and metabolism.'
'Given PTEN's dual
role, we were interested in understanding the metabolic profile of people with
Cowden syndrome. It was possible that mutations in PTEN could improve
The research team
conducted glucose tolerance tests with 15 volunteers with Cowden syndrome and
15 controls. People with Cowden syndrome had remarkably high insulin
sensitivity. Along with their colleagues at the Babraham Institute, the experts
revealed that it was due to raised activity in the insulin-signaling
The experts observed
that that body mass index of individuals with Cowden syndrome was more than
that of the controls. A comparison was drawn with a large group of over 2,000
volunteers from the Oxford Biobank, a data and tissue resource for research
established by Professor Fredrik Karpe.
This validated that
those with Cowden syndrome had more chances of obesity than the controls. The
additional body weight was responsible for the cause of excess fat and no
substantial differences were seen in where the fat was accumulated as compared
mentioned, 'This was a surprise. Normally insulin sensitivity goes with being
Dr Gloyn finally said,
'We now know that mutations that inactivate the PTEN gene result in increased
cancer risk and obesity, but also increase insulin sensitivity which is very
likely to protect against type 2 diabetes.
'The study shows how intimately the
biological pathways governing cell growth and metabolism are linked. We need to
thoroughly understand these pathways to identify which genes to target in the
development of new drugs.'
She further added, 'While there are promising
research avenues to pursue here, in the meantime the best way to avoid diabetes
remains exercising more and eating less.'
PTEN Mutations as a Cause of Constitutive
Insulin Sensitivity and Obesity; Aparana Pal et al; N Engl J Med 2012;