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Am J Physiol Renal Physiol 283: F286-F293, 2002. First published January 29, 2002; doi:10.1152/ajprenal.00330.2001
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Vol. 283, Issue 2, F286-F293, August 2002

Glucose stimulates O2 consumption, NOS, and Na/H exchange in diabetic rat proximal tubules

Andrew Baines and Patrick Ho

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5G 1L5

Endothelial nitric oxide synthase (NOS) and neuronal NOS protein increased in proximal tubules of acidotic diabetic rats 3-5 wk after streptozotocin injection. NOS activity (citrulline production) was similar in nondiabetic and diabetic tubules incubated with low glucose (5 mM glucose + 20 mM mannitol); but after 30 min with high glucose (25 mM), Ca-sensitive citrulline production had increased 23% in diabetic tubules. Glucose concentration did not influence citrulline production in nondiabetic tubules. High glucose increased carboxy-2-phenyl-4,4,5,5,-tetramethylimidazoline 1-oxyl-3-oxide (cpt10)-scavenged NO sevenfold in a suspension of diabetic tubules but did not alter NO in nondiabetic tubules. Diabetes increased ouabain-sensitive 86Rb uptake (141 ± 9 vs. 122 ± 6 nmol · min-1 · mg-1) and oligomycin-sensitive O2 consumption (QO2; 16.0 ± 1.7 vs. 11.3 ± 0.7 nmol · min-1 · mg-1). Ethylisopropyl amiloride-inhibitable QO2 (6.5 ± 0.6 vs. 2.4 ± 0.3 nmol · min-1 · mg-1) accounted for increased oligomycin-sensitive QO2 in diabetic tubules. NG-monomethyl-L-arginine methyl ester (L-NAME) inhibited most of the increase in 86Rb uptake and QO2 in diabetic tubules. L-NAME had little effect on nondiabetic tubules. Inhibition of QO2 by ethylisopropyl amiloride and L-NAME was only 5-8% additive. Uncontrolled diabetes for 3-5 wk increases NOS protein in proximal tubules and makes NOS activity sensitive to glucose concentration. Under these conditions, NO stimulates Na-K-ATPase and QO2 in proximal tubules.

oxygen consumption; nitric oxide synthase; sodium-hydrogen exchange; kidney; streptozotocin; oligomycin; ouabain; rubidium uptake; ketoacidosis; NG-monomethyl-L-arginine methyl ester; ethylisopropyl amiloride


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