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Diabetologia
Erschienen in: Diabetologia 6/2004

01.06.2004 | Article

Potent activation of multiple signalling pathways by C-peptide in opossum kidney proximal tubular cells

verfasst von: N. M. Al-Rasheed, F. Meakin, E. L. Royal, A. J. Lewington, J. Brown, G. B. Willars, N. J. Brunskill

Erschienen in: Diabetologia | Ausgabe 6/2004

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Abstract

Aims/hypothesis

Proinsulin C-peptide is generally believed to be inert without any appreciable biological functions. However, it has been shown to modulate a variety of cellular processes important in the pathophysiology of diabetic complications. We therefore investigated the ability of C-peptide to stimulate intracellular signalling pathways in kidney proximal tubular cells, the altered activation of which may possibly be related to the development of diabetic nephropathy.

Methods

Extracellular signal-regulated kinase (ERK) and Akt phosphorylation were evaluated by western blotting. ERK activity was measured by in vitro kinase assay. Intracellular Ca2+ was evaluated by confocal imaging. The membrane and cytosol-associated fractions of protein kinase C (PKC) isoforms were evaluated by western blotting. Proliferation was assessed by thymidine incorporation assay.

Results

Using the opossum proximal tubular kidney cell line as a model, we demonstrated that at high picomolar to low nanomolar concentrations, C-peptide stimulates extracellular signal-regulated mitogen-activated kinase (3.3±0.1-fold over basal at 3 minutes) and phosphatidylinositol 3-kinase (4.1±0.05-fold over basal at 5 minutes). ERK activation was attenuated by pre-treatment with a PKC inhibitor and abolished by pertussis toxin. Elevations of intracellular [Ca2+] are seen in response to 5 nmol/l C-peptide with consequent activation of PKC-α. Pre-treatment with pertussis toxin abolished PKC-α. C-peptide is also a functional mitogen in this cell type, stimulating significantly increased cell proliferation. Proliferation was attenuated by wortmannin and pertussis toxin pre-treatments. None of these effects is reproduced by scrambled C-peptide.

Conclusions/interpretation

This study provides evidence that C-peptide, within physiological concentration ranges, stimulates many signalling pathways in opossum kidney cells.
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Metadaten
Titel
Potent activation of multiple signalling pathways by C-peptide in opossum kidney proximal tubular cells
verfasst von
N. M. Al-Rasheed
F. Meakin
E. L. Royal
A. J. Lewington
J. Brown
G. B. Willars
N. J. Brunskill
Publikationsdatum
01.06.2004
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 6/2004
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1404-9

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