Genetic mutation identified for insulin sensitivity

The first single gene responsible for
insulin sensitivity in humans has been identified by researchers at the University
of Oxford. The discovery has implications for understanding type II diabetes.

A mutation was identified in a gene
which was previously known to put people at risk of developing type II diabetes - the tumor
suppressor phosphatase and tensin homologue (PTEN) gene. Mutations in this gene were also already associated with an increased risk of cancer.

Study leader Dr Anna Gloyn, of the
Oxford Centre for Diabetes Endocrinology and Metabolism, UK, told Fox News that
the research demonstrated 'a link between the cell cycle and a risk for type II
diabetes, which has started to suggest there might be a genetic overlap in
terms of your predisposition for getting diabetes and cancer'.

Insulin, the hormone which controls
the levels of glucose in blood, is produced, stored and released by cells of
the pancreas called beta cells. In type II
diabetes either the body does not produce enough insulin or the cells do not
respond to it, and this results in high levels of glucose in the blood.

To understand the role of the PTEN
gene, the team examined patients with a rare condition called Cowden syndrome, also
caused by a mutation of PTEN. A central feature of Cowden syndrome is the
development of non-cancerous,
tumor-like growths.

The researchers measured insulin sensitivity
and beta cell function in 15 patients and 15 healthy volunteers, and observed
how they metabolised glucose. The participants affected by Cowden syndrome
showed increased insulin sensitivity.

The paper, published in the New England
Journal of Medicine, concludes that these results 'support the hypothesis that
the epidemiologic and genetic associations between cancer and type II diabetes
may be based on common signaling pathways linking tumor-suppressor genes to
metabolic pathways that mediate insulin action'.

The researchers also noted that
patients with Cowden Syndrome were better at clearing glucose, but had a higher level
of obesity. This was a counterintuitive finding as the Cowden Syndrome patients,
with their greater sensitivity to insulin, should be able to clear glucose
faster.

'You would
think if we have insulin sensitive people they’d be thin', Dr Gloyn told Fox
News, 'but that wasn't the case'.

In
an editorial accompanying the paper, Dr Ulf Smith writes that scientists 'need
to know more about the role and complex regulation of PTEN activity in insulin-resistant
states in humans' and notes that the findings 'further underscore concerns that
[anti-cancer] therapeutic approaches aimed at increasing PTEN activity will
effect a decrease in insulin sensitivity and will increase the risk for type 2
diabetes'.