title: Proinsulin C-peptide abrogates type-1 diabetes-induced increase of renal endothelial nitric oxide synthase in rats.
abstract: 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.
  
  
  CONCLUSIONS
  The results indicate that C-peptide suppresses diabetes-induced abnormal renal eNOS expression, by which C-peptide may exert beneficial effects on diabetic nephropathy.
authors: Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors: Akihiro
authors: A
authors: Kamikawa
authors: Tatsuya
authors: T
authors: Ishii
authors: Kohei
authors: K
authors: Shimada
authors: Kennedy
authors: K
authors: Makondo
authors: Osamu
authors: O
authors: Inanami
authors: Naoki
authors: N
authors: Sakane
authors: Toshihide
authors: T
authors: Yoshida
authors: Masayuki
authors: M
authors: Saito
authors: Kazuhiro
authors: K
authors: Kimura
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D042783:Endothelial Cells / Q000201:enzymology*; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000201:enzymology*; D007678:Kidney Glomerulus / Q000473:pathology; D007700:Kinetics; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011384:Proinsulin / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D011384:Proinsulin; D019001:Nitric Oxide Synthase