Proinsulin C-peptide prevents type-1 diabetes-induced decrease of renal Na+-K+-ATPase alpha1-subunit in rats.
OBJECTIVE
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 alpha1-, alpha2- and beta3-subunits were investigated in the kidney of these rats.


RESULTS
Na(+)/K(+)-ATPase alpha1-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 alpha1-expression. The beta3-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 beta3-subunit did not appear to be affected by the diabetic state.


CONCLUSIONS
Diabetes selectively reduced Na(+)/K(+)-ATPase alpha1-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.
Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Lina
L
Nordquist
Kohei
K
Shimada
Tatsuya
T
Ishii
Daniela Tomie
DT
Furuya
Akihiro
A
Kamikawa
Kazuhiro
K
Kimura
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose; D002096:C-Peptide / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D000254:Sodium-Potassium-Exchanging ATPase