Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 365, Issue 1, pp 67–73 | Cite as

Human C-peptide acutely lowers glomerular hyperfiltration and proteinuria in diabetic rats: a dose-response study

  • Dan-Yang Huang
  • Kerstin Richter
  • Alexander Breidenbach
  • Volker Vallon
Original Article

Abstract.

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 1×. Application of 0.1, 0.3, 1, 3 or 10× 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.

Human C-peptide Diabetic rats Glomerular hyperfiltration Proteinurea 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Dan-Yang Huang
    • 1
  • Kerstin Richter
    • 1
  • Alexander Breidenbach
    • 2
  • Volker Vallon
    • 1
  1. 1.Department of Pharmacology, University of Tübingen, Wilhelmstrasse 56, 72074 Tübingen, Germany
  2. 2.Schwarz Pharma AG, Alfred-Nobel-Strasse 10, 40789 Monheim, Germany

Personalised recommendations