Human C-peptide acutely lowers glomerular hyperfiltration and proteinuria in diabetic rats: a dose-response study.
Recent studies suggested that C-peptide treatment of C-peptide-deficient patients with type I diabetes mellitus may present a new approach to prevent diabetic nephropathy. The present study further elucidated this concept by assessing the acute effect of human C-peptide application on kidney function in anesthetized rats with streptozotocin (STZ)-induced diabetes. Human C-peptide was applied as an i.v. bolus followed by continuous infusion of a fivefold dose per hour. A dose of 6 nmol/kg plus 30 nmol/kg per h is referred to as 1x. Application of 0.1, 0.3, 1, 3 or 10x to STZ-diabetic rats elicited mean plasma human C-peptide concentrations of 0.5, 5, 24, 75 and 225 nmol/l, respectively. Under basal conditions STZ-diabetic rats exhibited as expected an increase in glomerular filtration rate (GFR) by about 30%, which was associated with a lower total renal vascular resistance (RVR) and a rise in renal blood flow (RBF) as well as enhanced urinary protein excretion (UPE) of about 70% as compared with control rats. Human C-peptide dose-dependently lowered GFR and UPE in STZ-diabetic rats without altering blood glucose levels. No significant effect of human C-peptide on RBF or RVR could be detected, which may indicate an effect on glomerular ultrafiltration coefficient. Maximum effects of human C-peptide on the diabetes-induced rises in GFR and UPE established an inhibition of 40% and 50%, respectively. Half-maximum effects on GFR and UPE were observed at plasma concentrations of human C-peptide in the range of 0.5-5 nmol/l, which is relatively close to endogenous C-peptide levels in non-diabetic rats. Unresponsiveness of non-diabetic control rats to human C-peptide further indicated specific effects.
Huang
Dan-Yang
DY
Department of Pharmacology, University of Tübingen, Wilhelmstrasse 56, 72074 Tübingen, Germany.
Richter
Kerstin
K
Breidenbach
Alexander
A
Vallon
Volker
V
D000818:Animals; D002096:C-Peptide / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
D002096:C-Peptide