A study published today in the Journal of the Public Library of Science has identified five genetic variations associated with higher levels of the branched-chain amino acids isoleucine, leucine and valine. Through research using recombinant rat proteins, the researchers also found that these gene mutations are associated with an increased risk of type 2 diabetes.
A team led by the Department of Epidemiology at the University of Cambridge Medical Research Council (MRC) made use of large-scale genetic data and detailed measurements of branched-chain amino acids and their metabolites in more than 16,000 volunteers.
Branched chain amino acids play a fundamental role in human metabolism, and it is the basis of protein. Unlike the other 20 amino acids, they can't be produced by the human body. This means that their level depends entirely on external resources (food sources or dietary supplements) and the body's metabolic capacity.
Up to now, although higher circulating levels of branched-chain amino acids have been found to be associated with type 2 diabetes, no study has been able to determine whether the association is causal. This is important because if found to be causally related, dietary intake reductions or changes in the metabolism of these amino acids may help to prevent the growing prevalence of diabetes and the severity of the disease.
Researchers studied more than 10 million genetic variations in more than 16,000 men and women and found genetic differences in five human genomic regions associated with higher levels of circulating branched-chain amino acids. They then found that in 300,000 people, including 40,000 people with diabetes, those with genetic differences associated with higher levels of branched-chain amino acids were at higher risk of developing type 2 diabetes, providing strong evidence of causality.
The PPM1K gene has been found to have the strongest association with all three amino acid levels and a higher risk of developing diabetes, and can encode a known regulator that plays a pivotal role in the breakdown of branched-chain amino acids. This suggests that impaired decomposition of these amino acids may make individuals at higher risk of developing type 2 diabetes. Intervention on this pathway may reduce the risk of diabetes.
"Our results suggest that therapeutic strategies for the metabolism of branched-chain amino acids can help to reduce the risk of diabetes, which we already know about," said Claudia Langenberg, MD from the MRC Epidemiology Unit at the University of Cambridge. Clinical trials are now needed to determine whether drugs that break down on branched-chain amino acids can reduce the risk of type 2 diabetes. Flarebio provides superior recombinant proteins like recombinant ITGB1 at great prices.
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