Diabetes-induced activation of system y+ and nitric oxide synthase in human endothelial cells: association with membrane hyperpolarization

The Journal of Physiology
Luis SobreviaG E Mann

Abstract

1. The activity of the human endothelial cell L-arginine transporter (system y+) has been correlated with cGMP production (index of nitric oxide) and prostacyclin (PGI2) release in umbilical vein endothelial cells cultured from normal or gestational diabetic pregnancies. 2. In non-diabetic and diabetic cells, transport of L-arginine was Na+ and pH independent, inhibited by other cationic L-arginine analogues and unaffected by neutral amino acids. 3. Diabetes was associated with an increased Vmax for saturable L-arginine transport (4.6 +/- 0.13 vs. 9.9 +/- 0.5 pmol (microgram protein)-1 min-1, P < 0.01), but had no effect on initial rates of transport for L-serine, L-citrulline, L-leucine or 2-deoxyglucose. 4. In non-diabetic and diabetic cells, elevated K+ resulted in a concentration-dependent inhibition in the initial rates of transport for L-arginine and the membrane potential-sensitive probe tetra[3H]phenylphosphonium (TPP+). 5. When resting membrane potential was measured using the whole-cell patch voltage clamp technique, diabetic cells were hyperpolarized (-78 +/- 0.3 mV) compared with non-diabetic cells (-70 +/- 0.04 mV, P < 0.04). Accumulation of [3H]TPP+ was also increased in diabetic compared with non-diabetic cells. ...Continue Reading

Citations

Sep 10, 2014·Amino Acids·Rodrigo ManjarinNathalie L Trottier
Nov 22, 2011·Current Diabetes Reports·M GausterU Hiden
Apr 10, 2007·The Journal of Membrane Biology·E I ClossA Rotmann
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Mar 23, 2011·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Barbara BonacasaGiovanni E Mann
Mar 23, 2011·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Lopa Leach
Jul 24, 2013·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Enrique Guzmán-GutiérrezLuis Sobrevia
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Dec 31, 2002·Physiological Reviews·Giovanni E MannLuis Sobrevia
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