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Proinsulin C‐peptide prevents type‐1 diabetes‐induced decrease of renal Na + ‐K + ‐ATPase α1‐subunit in rats
Author(s) -
Nordquist Lina,
Shimada Kohei,
Ishii Tatsuya,
Furuya Daniela Tomie,
Kamikawa Akihiro,
Kimura Kazuhiro
Publication year - 2010
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1071
Subject(s) - medicine , endocrinology , proinsulin , streptozotocin , insulin , diabetes mellitus , protein subunit , kidney , chemistry , peptide , c peptide , stimulation , biology , biochemistry , gene
Aims/Hypothesis C‐peptide reduces renal damage in diabetic patients and experimental animal models. In vitro studies suggest that the renal effects of C‐peptide may, in part, be explained by stimulation of Na + /K + ‐ATPase activity. However, the responses of Na + /K + ‐ATPase expression in the kidney of diabetic animals to C‐peptide administration remain unclear. The aim of this study was to clarify the responses. Methods Type 1 diabetic rats were produced by injecting streptozotocin (STZ), and some of the rats were treated with either C‐peptide or insulin by the aid of an osmotic pump for 1 week. The mRNA expression and immunohistochemical localization of Na + /K + ‐ATPase α1‐, α2‐ and β3‐subunits were investigated in the kidney of these rats. Results Na + /K + ‐ATPase α1‐subunit was abundantly expressed in the medullary collecting ducts of control animals, but the expression was markedly decreased in the diabetic state with concomitant decrease in its mRNA expression. Similar decreases were observed in the insulin‐treated diabetic rats, whereas in the C‐peptide‐treated diabetic rats, there was no reduction in the α1‐expression. The β3‐subunit was expressed in podocytes and parietal cells in the glomeruli, vascular endothelial cells, and cortical collecting ducts, but lesser signals were observed in the proximal and distal tubules. However, the β3‐subunit did not appear to be affected by the diabetic state. Conclusions Diabetes selectively reduced Na + /K + ‐ATPase α1‐subunit expression and abundance. Chronic administration of C‐peptide prevented this decrease. This implies a role for C‐peptide in the long‐term regulation of Na + /K + ‐ATPase function. Copyright © 2010 John Wiley & Sons, Ltd.