Amino Acids as Pharmaco-Nutrients for the Treatment of Type 2 Diabetes

Evidence is accumulating showing amino acids to play a key regulatory role in numerous metabolic processes. Amino acids, and leucine in particular, can be applied as potent insulin secretagogues. These stimulating properties are not restricted to healthy humans, but are also effective in long-term diagnosed type 2 diabetes patients. Co-ingestion of amino acid/protein with carbohydrate substantially augments endogenous insulin release, accelerates blood glucose disposal, and improves post-prandial glucose homeostasis. Besides their function as precursors for protein synthesis, some amino acids are also able to stimulate protein anabolism in an insulin-independent manner. Branched chain amino acids (BCAA), and leucine in particular, are capable of activating the mRNA translational machinery through the mammalian target of rapamycin (mTOR), which represents an interesting molecular target for the prevention or reduction of elevated muscle proteolysis in uncontrolled type 2 diabetes. Protein and/or specific amino acid supplementation could help to reduce muscle proteolysis and/or to stimulate protein synthesis, leading to an improved muscle protein balance, which augments whole-body blood glucose disposal capacity. Besides the potential benefits of protein and/or amino acid supplementation, there is evidence showing hyperaminoacidemia to impair skeletal muscle insulin signaling. Understanding the mechanisms by which different amino acids can alter metabolic signaling will be of great value for the development of effective nutritional and/or pharmacological interventions to prevent and/or treat insulin resistance and/or type 2 diabetes. Studies investigating the benefits of long-term amino acid and/or protein supplementation in type 2 diabetes patients are warranted.