Rare genetic disorder provides clues to development of the pancreas

December 11, 2011

A rare genetic disorder has given researchers at the University of Exeter a surprising insight into how the pancreas develops. The finding provides a clue to how it may be possible to 'programme' stem cells – master cells in the body that can develop into specialised cells – to become pancreatic cells.

Pancreatic agenesis is a rare condition in which the body is unable to produce a . The pancreas plays an essential role in regulating levels of sugar (glucose) in the blood. It does this by the release of the hormone insulin, which is generated and released by cells known as . It also produces enzymes to help digest and absorb food.

Rare mutations in the genes PDX1 and PTF1A have previously been shown to cause pancreatic agenesis, but have only been identified in a handful of families affected by the condition. Until now, the underlying causes of most cases have been unknown.

In a paper published today in Nature Genetics, an international team of researchers led by scientists from the Peninsula College of Medicine and Dentistry at the University of Exeter report a mutation in the gene GATA6 found in fifteen out of twenty-seven individuals with pancreatic agenesis. The study, funded by organisations including the Wellcome Trust, Diabetes UK and the National Institute for Health Research, establishes a key role for GATA6 in the development of pancreatic cells.

The finding was particularly surprising as switching off the GATA6 gene in mouse models appeared to make no difference to the development of the pancreas.

Professor Andrew Hattersley from the Peninsula College of Medicine and Dentistry, said: "This rare genetic condition has provided us with a surprising into how the pancreas develops. What is it that programmes cells to become pancreatic beta cells? Our study suggests that GATA6 plays a very important role in this process and we hope this will help the crucial work to try and make beta-cells for patients with type 1 diabetes."

Whilst pancreatic agenesis is an extreme form of pancreatic dysfunction, far more common is diabetes. In type 1 diabetes, which generally develops in childhood, the immune system attacks and destroys pancreatic beta cells and the body is unable to regulate glucose levels, whilst in type 2 diabetes, the beta cells gradually decline until, usually during adulthood, they cease to function.

Professor Sian Ellard, also from Peninsula College of Medicine and Dentistry, added: "This discovery was possible because new sequencing approaches meant we could test all the genetic information in one go and because with the help of doctors throughout the world we were able to study 27 patients with a very rare condition."

Explore further: How insulin-producing cells develop -- new finding could help fight against diabetes

More information: Allen, HL et al. GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nature Genetics; e-pub 11 Dec 2011

Related Stories

Fat cells send message that aids insulin secretion

November 6, 2007

The body's fat cells help the pancreas do its job of secreting insulin, according to research at Washington University School of Medicine in St. Louis. This previously unrecognized process ultimately could lead to new methods ...

Insulin-releasing switch discovered

March 15, 2011

Johns Hopkins researchers believe they have uncovered the molecular switch for the secretion of insulin — the hormone that regulates blood sugar — providing for the first time an explanation of this process. In ...

Neural stem cell transplant may tackle diabetes

October 7, 2011

Researchers in Japan have discovered how a patient's neural stem cells could be used as an alternative source of the beta cells needed for a regenerative treatment for diabetes. The research, published in EMBO Molecular Medicine ...

Recommended for you

Face shape is in the genes

August 25, 2016

Many of the characteristics that make up a person's face, such as nose size and face width, stem from specific genetic variations, reports John Shaffer of the University of Pittsburgh in Pennsylvania, and colleagues, in a ...

Researchers discover otulipenia, a new inflammatory disease

August 22, 2016

National Institutes of Health researchers have discovered a rare and sometimes lethal inflammatory disease - otulipenia - that primarily affects young children. They have also identified anti-inflammatory treatments that ...

Solving the mystery of meningiomas reveals a surprise twist

August 23, 2016

In solving one mystery—the genetic roots of benign brain tumors called meningiomas—a team of scientists led by Yale researchers stumbled upon an even greater one: How is it possible that two of the mutations linked to ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.