Gene blockade could reverse type 2 diabetes: Study

Published on September 26, 2011 at 2:39 AM · No Comments

By Dr Ananya Mandal, MD

Australian scientists report that they may be on the brink of reversing type 2 diabetes after a genetic discovery. The finding centers on how a particular gene responds to high-fat diets by disrupting insulin production in the pancreas and triggering diabetes.

More than 700,000 Australians have type 2 diabetes, which has no cure and is caused by a combination of genetic and environmental factors such as being overweight, eating a poor diet and a lack of exercise. Type 2 diabetes, also known as adult-onset diabetes because it commonly affects older people, occurs when the pancreas cannot produce enough insulin to break down glucose, a vital function needed to supply energy to the body.

In people who follow a healthy diet and get plenty of exercise, the gene usually lays dormant allowing the pancreas to function normally and produce enough insulin. However, when people eat high-fat diets the gene “switches on” and disrupts beta cells inside the pancreas and their role in insulin production. Scientists at the Diabetes and Obesity Research Program at the Garvan Institute of Medical Research in Sydney, based their findings about the workings of the gene, known as ld1, on studies in mice and cell cultures in the laboratory.

Their next step is to test whether special drugs can block the gene from disrupting insulin production. The institute's Dr Ross Laybutt said while it was “a stretch” to say the research could lead to a cure for diabetes it was hoped the drugs could reverse the disease. He explained, “The drugs could help the beta cells continue to produce insulin and protect them from the effects of a high-fat diet. So even when you were having this high-fat diet your beta cells would be protected against the normal deterioration that occurs. That's the potential. You wouldn't have diabetes anymore because it only occurs when the beta cells fail to secrete enough insulin.”

Dr Laybutt found that when laboratory mice were fed high-fat diets the ld1 gene “switched on” and caused the mice to develop diabetes. However, when the mice were on high-fat diets but ld1 was blocked at the same time, they were protected from the disease. Further tests also confirmed that pancreatic tissue from diabetes patients contains high levels of ld1, which is already known to promote the growth of cancer cells.

Dr Laybutt said several genes were linked to diabetes but ld1 appeared to play a major role in the development of the disease. “This gene is a master regulator of the other genes that make the beta cells work properly…When ld1 switches on it directly affects other genes which confer the ability of the beta cells to secrete insulin. Fat in the diet also switches on the gene as well as high glucose and stress too,” he said.

Dr Laybutt's research was published online by the journal Diabetes today. Speaking on the connotations of the research on humans Laybutt said, “It would be a five to 10 year process. Establishing the clinical benefits of a drug and the safety of drugs takes a lot of time. It would be in that sort of time frame before there would be a marketable drug for Type 2 diabetes to target this gene.”

However, Professor Paul Zimmet, a diabetes research expert from Monash University’s Baker IDI Heart and Diabetes Institute, said there were likely to be many genes associated with Type 2 diabetes. “Id1 is one of many genes that have been implicated and may have a role in one form of Type 2 diabetes. As such, it may be an important discovery,” said Professor Zimmet, who was not involved in the study. “However, while I would wish that it is the total answer to the disease, it is unlikely to be the only important gene. This is a study in mice and to what extent the findings can be extrapolated to man will require confirmatory studies in humans.”

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