title: C-peptide induces human renal mesangial cell proliferation in vitro, activating Src-kinase, PI-3 kinase and ERK1/2.
abstract: BACKGROUND
  Elevated levels of C-peptide have been found in patients with insulin resistance and early type 2 diabetes. These patients are at greater risk to develop micro- and macrovascular complications. Since diabetic nephropathy involves glomerular hyperproliferation, the present study evaluates the role of C-peptide on human renal mesangial cell proliferation.
  
  
  RESULTS
  C-peptide induces proliferation of human renal mesangial cells in a concentration-dependent manner with a maximal 2.6±0.4-fold induction at 10 nmol/L (P<0.05 compared with unstimulated cells; n=6), as revealed by [3H]-thymidine incorporation experiments. The proliferative effect of C-peptide is prevented by Src-kinase inhibitor-PP2, PI-3 kinase inhibitor-LY294002, and the ERK1/2 inhibitor-U126. Moreover, C-peptide induces phosphorylation of Src, as well as activation of PI-3 kinase and ERK1/2. Furthermore, C-peptide induces cyclin D1 expression as well as phosphorylation of retinoblastoma protein (Rb).
  
  
  CONCLUSIONS
  These results demonstrate an active role of C-peptide on the proliferation of human renal mesangial cells in vitro involving PI-3 kinase and MAP kinase signaling pathways, suggesting a possible role of C-peptide in glomerular hyperproliferation in patients with diabetic nephropathy.
authors.affiliation: Department of Internal Medicine II, University of Ulm, Germany.
authors.forename: Dusica
authors.initials: D
authors.lastname: Vasic
authors.forename: Andreas
authors.initials: A
authors.lastname: Spyrantis
authors.forename: Renate
authors.initials: R
authors.lastname: Durst
authors.forename: Helga
authors.initials: H
authors.lastname: Bach
authors.forename: Sonja
authors.initials: S
authors.lastname: Vogt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rottbauer
authors.forename: Daniel
authors.initials: D
authors.lastname: Walcher
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D002096:C-Peptide / Q000378:metabolism* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D019938:Cyclin D1 / Q000096:biosynthesis; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D050527:Mesangial Cells / Q000166:cytology* / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002070:Butadienes; D002096:C-Peptide; D002867:Chromones; D019938:Cyclin D1; D048049:Extracellular Signal-Regulated MAP Kinases; D009025:Morpholines; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011743:Pyrimidines; D016160:Retinoblastoma Protein; D019061:src-Family Kinases; C412373:AG 1879; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one