High concentration of glucose inhibits glomerular endothelial eNOS through a PKC mechanism

Shaoyou Chu, H. Glenn Bohlen

Research output: Contribution to journalArticle

43 Scopus citations


Kidney glomeruli are important targets of diabetic nephropathy. We hypothesized a high concentration of glucose could suppress glomerular endothelial nitric oxide synthase (eNOS) by a protein kinase C (PKC) mechanism, as has been found in other tissues. Mouse kidney slices (150-200 μm) were bathed in Hanks' solution with 100 μM L-arginine and exposed to either 5 or 20-30 mM D-glucose. Immunofluorescence identified only eNOS in normal mouse glomeruli. Measurements of glomerular NO concentration with NO-sensitive fluorescent dye (4,5-diaminofluorescein diacetate) using confocal microscopy and NO-sensitive microelectrodes verified that resting glomeruli had active production of NO that was inhibited by NG-nitro-L-arginine methyl ester. High-concentration (20-30 mM) D-glucose inhibited 60-70% of the NO production within 15-30 min; L-glucose at the same concentration did not have any effect. Inhibition of PKC-β with 100 nM ruboxistaurin prevented eNOS suppression in high-glucose media. Activation of PKC with 100 nM phorbol ester also suppressed the glomerular NO concentration. We concluded that eNOS in the renal glomerular capillary endothelial cells is suppressed by activity of PKC at high-glucose concentrations comparable to those in diabetic animals and humans. The consequence is a rapid decline in the generation of NO in the glomerular endothelial cells in the presence of a high concentration of glucose.

Original languageEnglish (US)
Pages (from-to)F384-F392
JournalAmerican Journal of Physiology - Renal Physiology
Issue number3 56-3
StatePublished - Sep 1 2004


  • Confocal imaging
  • Endothelial nitric oxide synthase
  • Hyperglycemia
  • Microelectrode
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology

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