Study reveals gene behind insulin resistance
EU-funded researchers have identified a human genetic variant that raises the risk of developing type 2 diabetes. The findings add to our understanding of the factors behind the condition, and could lead to the development of new treatments. The study is published in the journal Nature Genetics. Type 2 diabetes arises when the body cannot produce enough insulin or does not respond to insulin correctly. If cells in the heart or muscles, for example, either do not get enough insulin or do not use it properly, they cannot get enough glucose from the blood to use as energy. So far, scientists have identified 18 genetic variants which raise a person's risk of developing type 2 diabetes. Most of these variants impair the ability of the pancreas to produce sufficient insulin. In this study, an international team of scientists identified the first genetic variant that appears to affect the ability of muscle cells to use insulin. The researchers found the variant by scanning the genomes of thousands of people, including both diabetic and non-diabetic individuals. Comparisons of the two groups revealed a single mutation that affects the activity of a gene called Insulin Receptor Substrate 1 (IRS1). The IRS1 gene produces a protein which tells cells when to take up glucose from the blood. 'IRS1 is the first inside the cell that gets activated by insulin,' explained Robert Sladek of McGill University and the Génome Québec Innovation Centre in Canada. 'It basically tells the rest of the cell, 'hey, insulin is here, start taking in glucose from the blood!' If IRS1 doesn't work, the whole process is disrupted.' In people with the newly discovered genetic variant, the activity of the IRS1 gene was reduced by 40%, effectively rendering the body's cells less sensitive to insulin and damaging their ability to make energy from glucose. 'We are very excited about these results - this is the first genetic evidence that a defect in the way insulin works in muscles can contribute to diabetes. Muscle tissue needs to make more energy using glucose than other tissues. We think developing a treatment for diabetes that improves the way insulin works in the muscle could really help people with type 2 diabetes,' commented Professor Philippe Froguel of the Department of Genomic Medicine at Imperial College London in the UK. 'It's possible that in diabetic patients, the signal to turn this gene on and off might be impaired,' added Dr Sladek. 'But we might be able to use one of the other pathways to turn it on.' The study was supported in part by four EU-funded projects: EURO-BLCS ('Biological, clinical and genetic markers of future risk of cardiovascular disease'), which is financed under the Quality of life and management of living resources Specific programme of the Fifth Framework Programme (FP5), as well as EUGENE2 ('European network on functional genomics of type 2 diabetes'), EXGENESIS ('Health benefits of exercise: identification of genes and signalling pathways involved in effects of exercise on insulin resistance, obesity and the metabolic syndrome') and EURODIA ('Functional genomics of pancreatic beta cells and of tissues involved in control of the endocrine pancreas for prevention and treatment of type 2 diabetes'), all of which are funded under the Life sciences, genomics and biotechnology for health Thematic area of the Sixth Framework Programme (FP6).