Abstract

1. Modulation of L-arginine transport (system y +) and release of nitric oxide (NO) and prostacyclin (PGI 2) by elevated glucose and insulin were investigated in human cultured umbilical vein endothelial cells. 2. Elevated glucose induced a time- (6-12 h) and concentration-dependent stimulation of L-arginine transport, which was reversible and associated with a 3-fold increase in intracellular cGMP accumulation (index of NO synthesis) and 75% decrease in PGI 2 production. 3. Elevated glucose had no effect on the initial transport rates for L-serine, L-citrulline, L-leucine, L-cystine or 2-deoxyglucose. 4. Resting membrane potential was unaffected by elevated glucose whereas basal intracellular [Ca 2+] increased from 65 ± 5 nM to 136 ± 16 nM. 5. Insulin induced a protein synthesis-dependent stimulation of L-arginine transport and increased NO and PGI 2 production in cells exposed to 5 mM glucose. 6. In cells exposed to high glucose, insulin downregulated elevated rates of L-arginine transport and cGMP accumulation but had no effect on the depressed PGI 2 production. 7. Our findings suggest that insulin's normal stimulatory action on human endothelial eel vasodilator pathways may be impaired under conditions of sustained hyperglycaemia.