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C‐peptide confers protection in renal cortical endothelial cells during Type I diabetes by preventing the phosphorylation of glucose‐6‐phosphate dehydrogenase
Author(s) -
Vejandla Himani L.,
Kothur Anand,
Dabkowski Erinne R.,
Hollander John M.,
Frisbee Jefferson C.,
Brock Robert W.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.971.12
Subject(s) - medicine , pentose phosphate pathway , endocrinology , phosphorylation , chemistry , peptide , diabetes mellitus , biochemistry , biology , enzyme , glycolysis
Previously we have shown that C‐peptide, a by‐product of insulin biosynthesis, improves renal peritubular capillary blood flow and reduces vascular oxidants. NADPH appears to be critical to this effect via the actions of numerous vasoprotective systems. We have found that diabetes results in a significant reduction in endothelial NADPH, that is subsequently restored with C‐peptide. We hypothesize that C‐peptide provides protection to renal cortical endothelial cells (RCEs) during type I diabetes by restoring the activity of glucose‐6‐phosphate dehydrogenase (G6PD), the principal source of NADPH synthesis. Our data show that RCEs from diabetic mice have diminished G6PD activity (p<0.05) and their treatment with C‐peptide restores its activity back to non‐diabetic levels (p<0.05). These changes in G6PD activity occurred with concomitant alterations in NADPH. Using 2‐D gel electrophoresis of RCE lysate coupled with immunoblotting for G6PD, we demonstrate that diabetic RCEs have a significant increase in G6PD phosphorylation. C‐peptide treatment reduced the magnitude of this phosphorylation in diabetic RCEs, which occurred concomitant to restored G6PD activity. These results suggest that improving the activity of endothelial G6PD, by preventing its phosphorylation, may be a potential mechanism by which C‐peptide confers protection to RCEs during type I diabetes. NIH R01 DK067582