Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells

Cell Mol Life Sci. 2002 Jul;59(7):1185-9. doi: 10.1007/s00018-002-8496-5.


Based on the findings that proinsulin C-peptide binds specifically to cell membranes, we investigated the effects of C-peptide and related molecules on the intracellular Ca2+ concentration ([Ca2+]i) in human renal tubular cells using the indicator fura-2/AM. The results show that human C-peptide and its C-terminal pentapeptide (positions 27-31, EGSLQ), but not the des (27-31) C-peptide or randomly scrambled C-peptide, elicit a transient increase in [Ca2+]i. Rat C-peptide and rat C-terminal pentapeptide also induce a [Ca2+]i response in human tubular cells, while a human pentapeptide analogue with Ala at position 1 gives no [Ca2+]i response, and those with Ala at positions 2-5 induce responses with different amplitudes. These results define a species cross-reactivity for C-peptide and demonstrate the importance of Glu at position 1 of the pentapeptide. Preincubation of cells with pertussis toxin abolishes the effect on [Ca2+]i by both C-peptide and the pentapeptide. These results are compatible with previous data on C-peptide binding to cells and activation of Na-,K+ATPase. Combined, all data show that C-peptide is a bioactive peptide and suggest that it elicits changes in [Ca2+]i via G-protein-coupled pathways, giving downstream enzyme effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Peptide / analogs & derivatives*
  • C-Peptide / pharmacology*
  • Calcium / metabolism*
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Humans
  • Kidney Tubules / cytology
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism*
  • Kinetics
  • Rats
  • Species Specificity


  • C-Peptide
  • Calcium