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Diabetes Issues
Gene Discovery Sparks Hope for Type 2 Diabetes Cure
By
May 19, 2016 - 2:49:01 PM

(HealthNewsDigest.com) - RESEARCHERS have identified the gene they believe is responsible for the onset of type 2 diabetes, sparking hope for treatments to prevent and possibly reverse the progressive condition.

The researchers from Flinders University in South Australia collaborated with international research teams from the United States, Sweden and the United Kingdom to narrow down the possible field of 5000 candidate genes to one, known asRCAN1.

Study leader and Flinders University cell physiologist Professor Damien Keating said a cross-referencing approach using genes from individuals with Down syndrome was crucial to the result.

Professor Keating said people with Down syndrome were prone to a range of health disorders, including diabetes, resulting from the overexpression of particular genes because Down syndrome occurred when people had an extra copy of chromosome 21.

"Many individuals with Down syndrome experience lower insulin secretion, mitochondrial dysfunction and increased oxidative stress in the insulin-producing beta cells of the pancreas, which are all conditions that also appear in people with type 2 diabetes," Professor Keating said.

To identify genes duplicated in Down syndrome that contribute to problems with insulin secretion, scientists screened the genes of four mouse models of the disorder - two had high blood sugar and two did not, with the variation enabling a short-list of 38 implicated genes to be identified.

The scientists then narrowed down the list by comparing it to genes overexpressed in beta cells from humans with type 2 diabetes.

"The comparison identified a single gene, RCAN1, which, when we overexpress it in mice, causes them to have abnormal mitochondria in their beta cells, produce less cellular energy and secrete less insulin in the presence of high glucose," Professor Keating says.

According to the World Health Organisation, the number of people with diabetes in 2014 was 422 million, up from 108 million in 1980. In 2012, an estimated 1.5 million deaths were directly caused by diabetes and another 2.2 million deaths were attributable to high blood glucose.

Type 2 diabetes, which accounts for the majority of diabetes cases, is a progressive condition in which the body becomes resistant to the normal effects of insulin and/or gradually loses the capacity to produce enough insulin in the pancreas. The cause of type 2 diabetes is unknown.

"Given that we've identified this gene as important for reducing insulin secretion in type 2 diabetes, we are now at a stage where we have a series of drugs that target RCAN1 and we are now going to test to find whether these drugs can improve insulation secretion in type 2 diabetes," Prof Keating said.

"We don't understand what changes in our pancreas or in our insulin secreting beta cells to cause that transition from just being insulin resistant and having metabolic syndrome to transitioning to full-blown type 2 diabetes.

"RCAN1, this gene we identified, is certainly a candidate now for that."

Prof  Keating said none of the available treatments for type 2 diabetes targeted the primary cause of the condition.

"All the drugs out there simply alleviate the symptoms," he said.

"So we have to test these drugs that we have because we feel like that may be able to go straight to the cause of the reduced insulin secretion that causes Type 2 diabetes ... prevent it and possibly reverse it."

South Australia's capital Adelaide has three long-standing public universities, Flinders UniversityUniversity of South Australia, and the University of Adelaide, each of which are consistently rated highly in the international higher education rankings.

The results of the study led by Prof Keating have been published in the international journal PLOS Genetics.

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