Another step on the road to a cure for diabetes may give hope to the world’s 171 million diabetes sufferers, thanks to collaboration between teams from McGill University and the University of California at San Francisco (UCSF). Diabetes is a chronic condition that occurs when the pancreas does not produce enough insulin because of the destruction or dysfunction of small clusters of cells, known as islets of Langerhans. However, the rest of the pancreas, which produces digestive enzymes (the exocrine system), remains intact and functioning.

It is known that during embryonic development, and in all likelihood throughout life, exocrine cells can transform to become islet cells and begin secreting insulin. Finding a way to activate this transformation holds great promise in terms of improved treatments for diabetes, but the genes involved are not thoroughly understood.

A team led by Constantin Polychronakos, of McGill’s Endocrine Genetics Laboratory at The Children’s Hospital site of the Research Institute of the McGill University Hospital Centre (RI-MUHC), used state-of-the-art technologies such as capture microarrays and highly parallel sequencing to examine a previously unstudied gene called RFX6. The team discovered mutations in this gene and found that these mutations are the cause of a rare syndrome of neonatal diabetes involving the complete absence of islets of Langerhans. The work is set to be published in the journal Nature.

Collaborator Michael German, of UCSF, showed the same outcome in animals – that mice, whose RFX6 genes had been artificially disrupted, develop exactly the same syndrome as found in human neonatal diabetes cases. Although this syndrome is an extremely rare cause of diabetes, knowledge of the gene involved may benefit all people suffering from diabetes.

“This discovery brings us closer to one day finding a cure for diabetes. Now that we know the RFX6 gene is crucial in the process of insulin production, the door is open to finding a cure through gene therapy or therapeutics that will create new islets out of cells from the rest of the pancreas,” said Polychronakos.

The study was funded by the Juvenile Diabetes Foundation.