Abstract 15199: L-Citrulline Supplementation Reduces Plasma Arginase Activity in Type 2 Diabetes Patients

Abstract

Vascular dysfunction is a major cause of morbidity and mortality in diabetic patients. Diabetes has been linked to elevated arginase and associated with vascular endothelial dysfunction. The pathological process is characterized by impaired endothelial cell production of nitric oxide (NO) and/or decreased NO bioavailability. NO is produced by activity of endothelial NO synthase (eNOS) on its substrate L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence increases in arginase activity can decrease arginine levels, reducing its availability to eNOS and decreasing NO production. We aimed to determine levels of plasma arginase activity in type 2 diabetic (T2DM) patients and the effects of L-citrulline, a natural arginase inhibitor, on inhibiting arginase activity in T2DM patients. We determined arginase activity levels in 62 T2DM patients and compared it to age matched healthy volunteers (ages 45-65). Our results show that arginase activity is 1.7 fold higher in T2DM patient’s plasma than healthy controls. Levels of arginase correlated with H1AC levels in diabetic patients r=0.81. Twenty five patients received L-citrulline supplements (2000 mg/day) for 1 month. Arginase activity was decreased 30% in T2DM patients after taking L- citrulline supplements. There was a modest improvement on H1Ac levels in these patients. The effect on L-citrulline on arginase activity was also measure in bovine aortic endothelial cells (BAECs) grown in high glucose (HG) conditions. HG (25mM, 72 hrs) caused a 2 fold increase in arginase activity in BAECs and decreased NO production by 40%. L-citrulline 100μM completely prevented the increase in arginase activity and restored NO production levels. These data indicate that inhibiting arginase activity can have therapeutic benefits in diabetic patients by preventing vascular dysfunction and maintaining NO levels.