PMID- 18493738
OWN - NLM
STAT- MEDLINE
DCOM- 20081118
LR  - 20220311
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 51
IP  - 8
DP  - 2008 Aug
TI  - Human C-peptide antagonises high glucose-induced endothelial dysfunction through 
      the nuclear factor-kappaB pathway.
PG  - 1534-43
LID - 10.1007/s00125-008-1032-x [doi]
AB  - AIMS/HYPOTHESIS: Endothelial dysfunction in diabetes is predominantly caused by 
      hyperglycaemia leading to vascular complications through overproduction of 
      oxidative stress and activation of the transcription factor nuclear factor-kappaB 
      (NF-kappaB). Many studies have suggested that decreased circulating levels of 
      C-peptide may play a role in diabetic vascular dysfunction. To date, the possible 
      effects of C-peptide on endothelial cells and intracellular signalling pathways 
      are largely unknown. We therefore investigated the effect of C-peptide on several 
      biochemical markers of endothelial dysfunction in vitro. To gain insights into 
      potential intracellular signalling pathways affected by C-peptide, we tested 
      NF-kappaB activation, since it is known that inflammation, secondary to oxidative 
      stress, is a key component of vascular complications and NF-kappaB is a 
      redox-dependent transcription factor. METHODS: Human aortic endothelial cells 
      (HAEC) were exposed to 25 mmol/l glucose in the presence of C-peptide (0.5 
      nmol/l) for 24 h and tested for expression of the gene encoding vascular cell 
      adhesion molecule-1 (VCAM-1) by RT-PCR and flow cytometry. Secretion of IL-8 and 
      monocyte chemoattractant protein-1 (MCP-1) was measured by ELISA. NF-kappaB 
      activation was analysed by immunoblotting and ELISA. RESULTS: Physiological 
      concentrations of C-peptide affect high glucose-induced endothelial dysfunction 
      by: (1) decreasing VCAM-1 expression and U-937 cell adherence to HAEC; (2) 
      reducing secretion of IL-8 and MCP-1; and (3) suppressing NF-kappaB activation. 
      CONCLUSIONS/INTERPRETATION: During hyperglycaemia, C-peptide directly affects 
      VCAM-1 expression and both MCP-1 and IL-8 HAEC secretion by reducing NF-kappaB 
      activation. These effects suggest a physiological anti-inflammatory (and 
      potentially anti-atherogenic) activity of C-peptide on endothelial cells.
FAU - Luppi, P
AU  - Luppi P
AD  - Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, 
      Children's Hospital of Pittsburgh, 3460 Fifth Avenue, Pittsburgh, PA 15213, USA. 
      luppip@pitt.edu
FAU - Cifarelli, V
AU  - Cifarelli V
FAU - Tse, H
AU  - Tse H
FAU - Piganelli, J
AU  - Piganelli J
FAU - Trucco, M
AU  - Trucco M
LA  - eng
GR  - 5K12 DK063704/DK/NIDDK NIH HHS/United States
GR  - DK 024021-24/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080521
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (C-Peptide)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Aorta
MH  - C-Peptide/*pharmacology
MH  - Cell Culture Techniques
MH  - Chemokine CCL2/metabolism
MH  - Endothelium, Vascular/drug effects/metabolism/*physiopathology
MH  - Glucose/antagonists & inhibitors/*pharmacology
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - NF-kappa B/*physiology
MH  - Oxidative Stress/drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Cell Adhesion Molecule-1/drug effects/genetics
EDAT- 2008/05/22 09:00
MHDA- 2008/11/19 09:00
CRDT- 2008/05/22 09:00
PHST- 2008/02/11 00:00 [received]
PHST- 2008/03/28 00:00 [accepted]
PHST- 2008/05/22 09:00 [pubmed]
PHST- 2008/11/19 09:00 [medline]
PHST- 2008/05/22 09:00 [entrez]
AID - 10.1007/s00125-008-1032-x [doi]
PST - ppublish
SO  - Diabetologia. 2008 Aug;51(8):1534-43. doi: 10.1007/s00125-008-1032-x. Epub 2008 
      May 21.