AKT2 gene and insulin resistance 28/5/04. By the Wellcome Trust Sanger Institute The first demonstration of a mutation in a human gene downstream in the signal pathway from the insulin receptor leading to insulin resistance and diabetes in some people.

In type 2 diabetes, tissues of the body are insensitive to the action of insulin, the hormone that acts to control sugar levels. In a study of patients with severe impairment of insulin action, a group of researchers led by Steve O'Rahilly and Inês Barroso has identified a new mutation in a gene called AKT2 that is responsible for the symptoms in affected individuals in one family.

Although it had been suspected that the AKT2 protein played a role in 'transmitting' the insulin signal to the cellular machinery to regulate sugar levels this had not been demonstrated in humans.

In the research published in the 28 May issue of the journal Science, Inês Barroso from the Wellcome Trust Sanger Institute and colleagues showed that the mutation affects a critical region of the AKT2 protein and that the mutated protein could not produce the signalling changes that the normal, 'wild-type' protein could.

Together with the family history and clinical data and the responses of the affected individual, the work is the first demonstration of a mutation in a human gene downstream in the signal pathway from the insulin receptor leading to insulin resistance and diabetes in some people.

One question the team are currently addressing is whether more subtle variations within AKT2, possibly in non-coding or controlling regions of the gene, may also affect susceptibility to more common types of type 2 diabetes. To address this they are currently examining common DNA variants that map within AKT2 and that flank the gene in large numbers of type 2 diabetics and matched control individuals. It is hoped that this search may reveal more common variants in AKT2 that are important in the disease.

Adapted from a news release by the Wellcome Trust Sanger Institute .

Links

George S et al. (2004) A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science 2004 304;1325-8. Abstract

Dr Inês Barroso, Wellcome Trust Sanger Institute, research page