The Effects of L-Arginine in Patients with Type 2 Diabetes by Experimental Methods and Molecular Dynamics Simulations

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One of the most important global health problems is diabetes mellitus (DM), which is a glucose metabolism disorder and causes various dangerous symptoms. Two types, type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are the dominant forms of DM. According to estimations, in 2013, 382 million people had DM, of which about 90% were T2DM cases. In the present study, primarily, interventional, and experimental studies on 45 patients with T2DM were occupied and the effects of limited and controlled diet, metformin, and insulin in the presence or absence of L-Arginine were assessed on some blood biochemical parameters. Experimental data showed that the combination of metformin/L-Arginine or insulin/L-Arginine treatments can decrease fasting blood glucose. 2-hour glucose of patients’ serums was reduced in all three treated groups. L-Arginine in combination with insulin decreases insulin resistance and increases insulin sensitivity in patients with T2DM. Glut 4, which is not seen in the lymphocytes of T1DM patients or healthy individuals, was found in the patient’s peripheral lymphocytes. L-Arginine supplementation in all 3 groups led to a decrease in the level of mRNA of GLUT 4, and also it’s trafficking from cytosol to plasma membrane. Furthermore, the structural change of nitric oxide synthase (NOS) in the absence and presence of metformin was investigated by molecular dynamics (MD) simulation. MD data revealed that in the presence of metformin, L-Arginine is run away from the NOS active site. So, the conversion of L-Arginine to NO can be decreased. On the other side, overproduction of NO by NOS leads to pathological conditions in stroke and shock, and the medication by metformin could be assigned worthwhile.