Compounds are already being developed for blocking the gene – known as Id1 – as it has known adverse effects in cancer. This drug development work would very much shorten the path from discovery to prospective treatment in the case of diabetes.
Type 2 diabetes occurs when the body becomes less able to produce and use insulin, a hormone essential for maintaining normal metabolism of food. The disorder is associated with a high-sugar, high-fat diet combined with lack of exercise.
Insulin is produced in the pancreas by highly specialised ‘beta cells’, and then carried around our bodies in the bloodstream, helping cells metabolise food.
While all cells in our bodies contain the same DNA, different cells ‘express’ different genes, depending on their function. Beta cells predominantly express genes that help them secrete insulin.
When diabetes develops, the gene expression pattern in a beta cell changes, ultimately making the cell incapable of doing its job.
PhD scholar Mia Akerfeldt and Dr Ross Laybutt from Sydney’s Garvan Institute of Medical Research have found that Id1 appears to be the master regulator of other genes in a beta cell, and it is ‘switched on’ when people consume a high fat diet. This finding is reported in the journal Diabetes, now online.
“We’re saying that Id1 is the molecular link between environmental factors, such as high fat diet, and beta cell dysfunction,” said Dr Laybutt.
“Not only does the presence of Id1 appear to initiate all the other gene expression changes that take place in dysfunctional beta cells, its absence completely protects the beta cell.”
“We’ve demonstrated our finding in animal models and cell culture, and we’ve also shown that pancreatic tissue from diabetic people expresses Id1.”
Laybutt and team intend to treat diabetic mice with the chemical compound already in development to block Id1 in cancer. If they can delay diabetes or improve insulin secretion in mice, they believe there is new hope for people with diabetes.
“If Id1 inhibitors are shown to be safe in clinical trials for cancer, I see no reason why they should not also be trialled for diabetes,” said Laybutt.
The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent’s Hospital in Sydney, it is now one of Australia’s largest medical research institutions with over 500 scientists, students and support staff. Garvan’s main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan’s mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan’s discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.
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