ACTIVATION OF L-ARGININE TRANSPORT (SYSTEM Y(-OXIDE SYNTHASE BY ELEVATED GLUCOSE AND INSULIN IN HUMAN ENDOTHELIAL-CELLS()) AND NITRIC)

1. Modulation of L-arginine transport (system y(+)) and release of nit ric oxide (NO) and prostacyclin (PGI(2)) by elevated glucose and insul in were investigated in human cultured umbilical vein endothelial cell s. 2. Elevated glucose induced a time- (6-12 h) and concentration-depe ndent stimulation of L-arginine transport, which was reversible and as sociated with a 3-fold increase in intracellular cGMP accumulation (in dex of NO synthesis) and 75% decrease in PGI(2) production. 3. Elevate d glucose had no effect on the initial transport rates for L-serine, L -citrulline, L-leucine, L-cystine or 2-deoxyglucose. 4. Resting membra ne potential was unaffected by elevated glucose whereas basal intracel lular [Ca2+] increased from 65 +/- 5 nM to 136 +/- 16 nM. 5. Insulin i nduced a protein synthesis-dependent stimulation of L-arginine transpo rt and increased NO and PGI(2) production in cells exposed to 5 mM glu cose. 6. In cells exposed to high glucose, insulin downregulated eleva ted rates of L-arginine transport and cGMP accumulation but had no eff ect on the depressed PGI(2) production. 7. Our findings suggest that i nsulin's normal stimulatory action on human endothelial cell vasodilat or pathways may be impaired under conditions of sustained hyperglycaem ia.