Down Syndrome helps identify diabetes gene

Australian scientists have used the genetics of people with Down Syndrome to identify a single gene that may cause type 2 diabetes, potentially paving the way for new drug therapies.

Their approach could be used to investigate the genetic causes of other maladies such as congenital heart defects and Alzheimer’s disease.

A team of international scientists, led by Professor Damien Keating from Adelaide's Flinders University, examined genes from individuals with Down Syndrome to identify a single gene, called RCAN1, responsible for defective insulin secretion in the beta cells in the pancreas. The study was published today in PLOS Genetics.

“We thought that because Down Syndrome is caused by an extra copy of chromosome 21, it may be that there are genes on chromosome 21 that can cause beta cell dysfunction and might be relevant to type 2 diabetes,” Prof Keating, an expert in cell physiology, tells SBS.

Down Syndrome occurs when people have a third copy of chromosome 21, which can cause a whole array of health problems, including both type 1 and type 2 diabetes.

Diabetes is one of the fastest growing chronic conditions in Australia. Of the 1.7 million Australians who are diabetic, an estimated 85 per cent have type 2 diabetes.

“In type 2 diabetes, we all know that obesity is a significant risk factor, but there are plenty of people in the population that are obese that never develop type 2 diabetes,” says Prof Keating.

He explains the researchers used a cross-referencing approach to narrow down the search from the initial field of 5000 candidates, suggested by a prior study, to a list of 38 genes that showed activity in the Down Syndrome mouse models.

They then looked at which of those 38 genes showed increased expression in the beta cells in humans with type 2 diabetes and came up with a single candidate – RCAN1.

“We went and tested whether increasing the amount of RCAN1 in beta cells can cause the sort of changes that are seen in Type 2 diabetes, and that’s exactly what we did see.”

Prof Keating adds, “We think that this is directly translatable to human models and what we’re now in the process of starting is we’ve identified a series of drugs that inhibit RCAN1. We want to now test whether or not they can improve insulin secretion when we’re over-expressing RCAN1.”

Current treatments for type 2 diabetes focus on managing the symptoms rather than targeting the cause, but this breakthrough could allow scientists to design drugs to specifically target RCAN1 in beta cells and allow the pancreas to start producing and secreting adequate levels of insulin again.

“Our approach is novel in that, if successful, we would actually be treating the cause or significant cause of type 2 diabetes by improving insulin output and potentially reversing the beta cell dysfunction.”

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