Proinsulin C-peptide abrogates type-1 diabetes-induced increase of renal endothelial nitric oxide synthase in rats.
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.
Kamikawa
Akihiro
A
Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Ishii
Tatsuya
T
Shimada
Kohei
K
Makondo
Kennedy
K
Inanami
Osamu
O
Sakane
Naoki
N
Yoshida
Toshihide
T
Saito
Masayuki
M
Kimura
Kazuhiro
K
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
D001786:Blood Glucose; D002096:C-Peptide; D011384:Proinsulin; D019001:Nitric Oxide Synthase