L-arginine transport in retinas from streptozotocin diabetic rats: correlation with the level of IL-1 beta and NO synthase activity

Several evidences suggest that the pro-inflammatory cytokines IL-1 beta and the radical NO are implicated as effecters molecules in the pancreatic bet a-cells dysfunction; an event preceding the pathogenesis of diabetes. IL-1 beta induces the expression of the inducible isoform of NO synthase (iNOS), which use L-arginine as substrate to overproduce NO. However, it is not kn own whether these events may participate in the development of diabetic ret inopathy, which is the main cause of blindness. In this work, we found an i ncreased level of IL-1 beta in retinas from streptozotocin-induced (STZ) di abetic rats. We also observed that the activity of the NO synthase (NOS) an d the L-arginine uptake are enhanced in retinas from STZ-induced diabetic r ats as compared to retinas from control rats. We found that the uptake of L -arginine in retinas from control and diabetic rats occurs through a transp orter resembling the Y + system, i.e. it is saturable, not affected over th e pH range 6.5 to 7.4, and is independent of the extracellular Na+. Neverth eless, the L-arginine transport in retinas from diabetic rats occurs throug h a carrier with lower affinity (K-m = 25 mu M) and higher capacity (V-max = 295 +/- 22.4 pmol L-arginine/mg protein) than in retinas from control rat s (K-m = 5 mu M and V-max = 158 +/- 12.8 pmol L-arginine/mg protein) which is correlated with the increased NOS activity and consequent depletion of t he intracellular pool of L-arginine. (C) 1999 Elsevier Science Ltd. All rig hts reserved.