Autogen presents diabetes findings at Brazil conference

The discovery of a gene that links type 2 diabetes and heart disease could lead to the development of new therapeutic treatments for diabetes, according to Victorian biotech Autogen.

Autogen's CEO, Prof Greg Collier, presented the research at the International Congress on Obesity in Sao Paulo, Brazil on Wednesday.

Autogen scientists originally identified the gene, known as Tanis, in Israeli sand rats, a model for obesity and type 2 diabetes. Subsequently, a similar gene has been identified in humans.

According to Collier, the Tanis gene encodes a unique membrane protein that is found on both the cell surface and the intracellular membranes of all cells.

"It is not a member of a known gene family and we have proven that it is a binding protein that binds to serum amyloid A (SAA), a major circulating protein involved in the inflammation response and also associated with diabetes and obesity," said Collier in an email to Australian Biotechnology News.

By over-expressing the Tanis protein in human liver cells, the researchers have shown that the cells develop symptoms of diabetes, with a decrease in glucose uptake and a decrease in glycogen synthesis and decreased insulin sensitivity to these glucose pathways including gluconeogenesis.

Collier said that these changes were consistent with Tanis causing insulin resistance in human liver cells, and were similar to changes seen in the liver of a diabetic.

"The diabetic liver is insulin resistant - Tanis causes liver insulin resistance - this is a major new finding," said Collier.

The discovery of the Tanis gene, which has been protected by a provisional patent, now allows Autogen and its partner Merck Sante to start looking at possible therapeutics targeting the gene.

"Because we now know that increased Tanis causes insulin resistance and we have evidence for the proteins that bind to Tanis - the therapy would be aimed at reducing the effects of Tanis - an antagonist to Tanis action," explained Collier.

Internationally renowned diabetes expert Prof Paul Zimmet, who chairs Autogen's scientific advisory board, said that Tanis was an important Australian and international discovery.

"This is very exciting and a world first - it is the first time a gene has been discovered linking type 2 diabetes, heart disease and inflammation, all considered part of a cluster of high heart risk. In addition, it may have important implications for the treatment of Alzheimer's and arthritis," Zimmet explained.

He said that it provided a major new drug target for both diabetes and heart disease and linked the two conditions beautifully. Zimmet also noted that amyloid proteins were implicated in diseases including Alzheimer's and arthritis.

"The fact that the protein causes insulin resistance in liver cells is very important as insulin resistance is the main defect in type 2 diabetes. Therefore any drug developed from this is important for both diabetes and heart disease," Zimmet said.

In addition to the Tanis gene, Autogen has identified and filed provisional patent applications for another 40 genes associated with obesity and type 2 diabetes, including the Beacon gene, which appear to regulate food intake.