C-peptide stimulates rat renal tubular Na+, K(+)-ATPase activity in synergism with neuropeptide Y

Diabetologia. 1996 Feb;39(2):199-205. doi: 10.1007/BF00403963.


This study was performed in order to test the hypothesis that the connecting peptide of proinsulin, C-peptide, might in itself possess biological activity. Renal tubular Na+, K(+)-ATPase, which is a well-established target for many peptide hormones, was chosen as a model. Rat C-peptide (I) was found to stimulate Na+, K(+)-ATPase activity in single, proximal convoluted tubules dissected from rat kidneys. C-peptide increased the Na+ affinity of the enzyme and all subsequent studies were performed at non-saturating Na+ concentrations. C-peptide stimulation of Na+, K(+)-ATPase activity occurred in a concentration-dependent manner in the dose range 10(-8)-10(-6) mol/l. The presence of neuropeptide Y, 5 x 10(-9) mol/l, enhanced this effect and stimulation of Na+, K(+)-ATPase activity then occurred in the C-peptide dose range 10(-11)-10(-8) mol/l. C-peptide stimulation of Na+, K(+)-ATPase activity was abolished in tubules pretreated with pertussis toxin. It was also abolished in the presence of FK 506, a specific inhibitor of the Ca2(+)-calmodulin-dependent protein phosphatase 2B. These results indicate that C-peptide stimulates Na+, K(+)-ATPase activity, probably by activating a receptor coupled to a pertussis toxin-sensitive G-protein with subsequent activation of Ca2(+)-dependent intracellular signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Calcium / metabolism
  • Cells, Cultured
  • Drug Synergism
  • In Vitro Techniques
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / enzymology
  • Kidney Tubules, Proximal / metabolism*
  • Kinetics
  • Male
  • Neuropeptide Y / pharmacology*
  • Pertussis Toxin
  • Rats
  • Rats, Sprague-Dawley
  • Sodium / metabolism
  • Sodium-Potassium-Exchanging ATPase / drug effects
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Tacrolimus / pharmacology
  • Virulence Factors, Bordetella / pharmacology


  • Neuropeptide Y
  • Virulence Factors, Bordetella
  • Sodium
  • Pertussis Toxin
  • Sodium-Potassium-Exchanging ATPase
  • Calcium
  • Tacrolimus