Introduction
DM
TYPE 2 DIABETES MELLITUS
Metformin is a key drug in treatment of type 2 diabetes mellitus (DM) [Understanding of regulation of amino acids by metformin could however potentially resolve more than one of the remaining uncertainties concerning metformin. Firstly, involvement of BCAA in metformin action might account for some of the discrepancy between effective doses of drug Secondly, regulation of BCAA could clarify the effect of metformin on hepatocyte glucose production. Evidence has been gathering for decades that glucagon, besides being a counterregulatory hormone, has an additional regulatory role in amino acid metabolism [Finally, regulation of amino acids could play a role in actions of metformin on cardiac health, which remain poorly understood. It has long been known that metformin inhibits mTOR signaling, which is a pathway activated by amino acids including the BCAA leucine [These considerations have led us in the current study to use multiple approaches, including human studies, to define the role of BCAA in therapeutic action of metformin.