Faulty Amino Acid Metabolism Increases Risk of Type-2 Diabetes

Highlights

Five genetic variants associated with higher levels of branched-chain amino acids have been found.
These variants affect the metabolism of the branched-chain amino acids.
Faulty metabolism puts an individual at the risk of developing type-2 diabetes

Five genetic variants associated with higher levels of the branched-chain amino acids isoleucine, leucine and valine, has been identified by a study published in the journal PLOS Medicine.

The researchers also found that these genetic variants were associated with an increased risk of type 2 diabetes.

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‘Treatment strategies which target metabolism of branched-chain amino acids could help to reduce the risk of diabetes.’

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The researchers, led by the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, used large-scale genetic data together with detailed measurements of the branched-chain amino acids and their metabolites in the blood of more than 16,000 volunteers.

Branched-Chain Amino Acids-

Amino acids play a crucial role in human metabolism and are the building block of proteins. There are 20 different types of amino acid in the body.

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Branched-chain amino acids are different from other amino acids. The three amino acids in this category are isoleucine, leucine and valine. They metabolize different from the other amino acids.

They cannot be made by the human body. This means that their levels depend entirely on external sources, from food sou

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rces or dietary supplements, and the ability of our body to metabolize them. They are highly predominant in the muscle tissue and are important for muscle protein synthesis.

They help to protect muscles from exercise-induced protein breakdown by increasing the availability of carbohydrates. They can be oxidized in the muscles for energy during exercise.

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Causal Link to Type 2 Diabetes-

To date, while higher circulating levels of branched-chain amino acids have been found to be associated with type 2 diabetes, no study has been able to establish whether this link is causal.

This is important, because if the relationship is found to be causal, reducing dietary intake or altering the metabolism of these amino acids could help to prevent diabetes, an increasingly common and serious disease.

Study of Genetic Variants-

The researchers studied over 10 million genetic variants in more than 16,000 men and women and discovered five regions of the human genome with genetic differences that are associated with higher levels of circulating branched-chain amino acids.

In 300,000 individuals, including 40,000 diabetes patients, those carrying the genetic differences associated with higher levels of branched-chain amino acids were also found to be at increased risk of type 2 diabetes, providing strong evidence of a causal link.

PPM1K, the gene found to be most strongly associated with levels of all three amino acids and also with a higher risk of diabetes, encodes a known regulator of the key step in the breakdown of branched-chain amino acids.

This suggests that an impaired breakdown of these amino acids may put individuals at higher risk of type 2 diabetes. Intervening on this pathway may reduce diabetes risk.

"Our results suggest that treatment strategies which target metabolism of branched-chain amino acids could help to reduce the risk of diabetes, and we already know which molecules target this metabolic pathway", says Dr Claudia Langenberg from the MRC Epidemiology Unit at the University of Cambridge.

Clinical trials will now need to be carried out to establish if drugs that target the breakdown of branched-chain amino acids can reduce the risks of type 2 diabetes.

References

Branched-chain amino acid supplementation does not enhance athletic performance but affects muscle recovery and the immune system. - (https://www.ncbi.nlm.nih.gov/pubmed/18974721)

Source-Medindia