The most frequent alterations in plasma amino acid concentrations in type 1 and type 2 diabetes are decreased L-serine and increased branched-chain amino acid (BCAA; valine, leucine, and isoleucine) levels. The likely cause of L-serine deficiency is decreased synthesis of 3-phosphoglycerate, the main endogenous precursor of L-serine, due to impaired glycolysis. The BCAA levels increase due to decreased supply of pyruvate and oxaloacetate from glycolysis, enhanced supply of NADH+H⁺ from beta-oxidation, and subsequent decrease in the flux through the citric acid cycle in muscles. These alterations decrease the supply of α-ketoglutarate for BCAA transamination and activity of branched-chain keto acid dehydrogenase, the rate-limiting enzyme in BCAA catabolism. L-serine deficiency contributes to impaired synthesis of sphingolipids and increased synthesis of deoxysphinganines, which play a role in pathogenesis of diabetic neuropathy, impaired homocysteine disposal via methionine cycle and transsulfuration pathway resulting in hyperhomocysteinemia, and glycine deficiency due to the adaptive increase in glycine utilization for L-serine synthesis. Enhanced BCAA levels contribute to increased levels of aromatic amino acids (phenylalanine, tyrosine, and tryptophan), insulin resistance, and accumulation of various metabolites whose influence on the progression of diabetes has not been clarified. Due to positive effects of BCAA on protein balance, it is not clear whether their increased levels in diabetes are beneficial or harmful. It is concluded that:

·   Plasma amino acid concentrations should be monitored in all patients with diabetes. In the case of the decrease in serine and glycine levels, their supplementation should be recommended.

·   The ratio between BCAA and L-serine levels could be a better prognostic indicator of insulin deficiency or resistance than BCAA alone.

·   Better understanding of the consequences of perturbations in BCAA metabolism is essential for making decisions regarding their dietary recommendations in patients with diabetes.

Keywords:  branched-chain amino acids; serine; glycine; insulin resistance.   

Financial Support: Charles University, the Cooperatio Program, research area METD.  

Milan Holeček obtained M.D. degree in 1981 from Charles University in Prague. He completed his Ph.D. degree in physiology in 1985 studying the possibilities of nutritional modulation of liver regeneration. In 1991 he was awarded the fellowship which took him to the laboratory of Professor Adibi in the Department of Clinical Nutrition at the University of Pittsburgh, PA, USA. Here he began investigation of metabolism of amino acids in catabolic states. This work has continued to date.  In 2009 he was appointed to Professor of Physiology. He has published more than 100 papers in reputed journals. Successfully supervised 4 Ph.D. students.  H-index = 27.