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Proinsulin C‐peptide Reduces Oxygen Consumption (QO2) in Isolated Kidney Proximal Tubular (PT) Cells from Diabetic Rats
Author(s) -
Nordquist Lina,
Fasching Angelica,
Palm Fredrik
Publication year - 2007
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.21.6.a1333-b
Subject(s) - medicine , endocrinology , chemistry , peptide , kidney , c peptide , ouabain , diabetes mellitus , sodium , biology , biochemistry , organic chemistry
Electrolyte transport by the Na + /K + ‐ATPase in PT cells contributes to a majority of the total kidney QO 2 . Therefore, a diabetes‐induced increase in Na + /K + ‐ATPase activity will influence the QO 2 and possibly limit the oxygen availability in the kidney. C‐peptide has been shown to have renoprotective effects, and we investigated the effect of C‐peptide on QO 2 in PT cells isolated from normoglycemic and streptozotocin‐induced diabetic rats. QO 2 was measured in untreated cells and in and cells pretreated with C‐peptide (5 nmol/l). The effect on transport‐independent QO 2 was investigated in cells pretreated with ouabain. Diabetic cells had increased baseline QO 2 compared to controls (38±3, n=9 vs. 29±3 nmol·mg protein −1 ·min −1 , n=6; P<0.05). C‐peptide normalized QO 2 in diabetic cells (28±4 nmol·mg protein −1 ·min −1 , n=8), but had no effect on control cells (28±6 nmol·mg protein −1 ·min −1 , n=6). The transport‐independent QO 2 was higher in diabetic cells (21±3, n=7 vs. 14±3 nmol·mg protein −1 ·min −1 , n=7; P<0.05) and C‐peptide reduced QO 2 only in the diabetics (17±3 nmol·mg protein −1 ·min −1 , n=8; P<0.05). In conclusion, C‐peptide normalizes oxygen consumption in PT cells isolated from diabetic rats, which is mediated via direct effects on Na + /K + ‐ATPase, as well as reduced transport‐independent QO 2 . This might explain the beneficial effects of C‐peptide on kidney function when given to diabetics.