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Proinsulin C‐peptide abrogates type‐1 diabetes‐induced increase of renal endothelial nitric oxide synthase in rats
Author(s) -
Kamikawa Akihiro,
Ishii Tatsuya,
Shimada Kohei,
Makondo Kennedy,
Inanami Osamu,
Sakane Naoki,
Yoshida Toshihide,
Saito Masayuki,
Kimura Kazuhiro
Publication year - 2007
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.810
Subject(s) - proinsulin , medicine , enos , endocrinology , diabetic nephropathy , insulin , nitric oxide synthase , diabetes mellitus , c peptide , nitric oxide , endothelium , nitric oxide synthase type iii , type 2 diabetes , nephropathy , kidney , chemistry
Background Proinsulin C‐peptide shows ameliorative effects on diabetic complications, possibly through the production of nitric oxide (NO). On the contrary, increased local availability of NO and expression of endothelial NO synthase (eNOS) in the renal endothelium are shown to be involved in the progression of diabetic nephropathy. The aim of this study was to elucidate the effect of C‐peptide and insulin as a reference on the eNOS expression in the early phase of type 1 diabetic rat kidney. Methods Type 1 diabetes in rats was produced by streptozotocin injection and some of the rats were treated with either C‐peptide or insulin by the aid of an osmotic pump for 1 week. Conventional biochemical and histological analyses were performed on tissue samples. Results The diabetic rats showed hyperglycemia with over 90% reduction of endogenous insulin and C‐peptide. Replacement with C‐peptide or insulin resulted in recovery of weight lost, but only insulin infusion lowered plasma‐glucose concentration. The eNOS protein was localized in glomeruli and endothelial cells of arterioles, and its amounts in the kidneys, but not in the lungs, of diabetic rats was increased. Replacement with C‐peptide or insulin‐abrogated diabetes‐induced increase of renal eNOS protein. Conclusion The results indicate that C‐peptide suppresses diabetes‐induced abnormal renal eNOS expression, by which C‐peptide may exert beneficial effects on diabetic nephropathy. Copyright © 2007 John Wiley & Sons, Ltd.