February 1, 2012

Body Clock Receptor Linked to Diabetes

(Ivanhoe Newswire) — Your body talks. It tells you when you're hungry and it tells you when you're tired. The body's sleep-wake cycle is controlled by the hormone melatonin. Melatonin regulates the body´s release of insulin, which in turn regulates the body´s blood sugar level. In 2008, a genetic study led by Imperial College London discovered that people with common variations in the gene for MT2, a receptor for melatonin, have a slightly higher risk of being diagnosed with type 2 diabetes.

Previous research found that people who work night shifts have a higher risk of type 2 diabetes and heart disease. Studies have also found that if volunteers have their sleep disrupted repeatedly for three days, they temporarily develop symptoms of diabetes.

Professor Philippe Froguel, from the School of Public Health at Imperial College London along with his Imperial team collaborated with several individuals from institutions in the UK and France to examine the MT2 gene in 7,632 people. They looked for more unusual variants that have a bigger effect on disease risk. What they found was 40 variants associated with type 2 diabetes, four of which were very rare and rendered the receptor completely incapable of responding to melatonin. The scientists then confirmed the link with these four variants in an additional sample of 11,854 people.

Froguel and his team analyzed each mutation by testing what effect they would have on the MT2 receptor in human cells in a lab. The mutations that completely prevented the receptor from working proved to have a very big effect on diabetic risk, suggesting that there is a direct link between MT2 and the disease.

The study also revealed that carrying any of the four rare mutations in the MT2 gene increased a person's risk of developing type 2 diabetes six times. The researchers suggested that mutations in the MT2 gene may disrupt the link between the body clock and insulin release, leading to abnormal control of blood sugar.

"We found very rare variants of the MT2 gene that have a much larger effect than more common variants discovered before. Although each mutation is rare, they are common in the sense that everyone has a lot of very rare mutations in their DNA. Cataloguing these mutations will enable us to much more accurately assess a person's risk of disease based on their genetics," Froguel was quoted as saying.

The findings should help scientists to more accurately assess personal diabetes risk and could lead to the development of personalized treatments.

SOURCE: Imperial College London, January 2012