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High glucose promotes the release and expression of novel vasoactive peptide, coupling factor 6, in human umbilical

Xiaolu Li1, Shanshan Xing, Like Zhang

  • 1Shandong University School of Medicine, Ji'nan 250012, China.

Peptides
|December 19, 2006
PubMed

Insights

High glucose levels increase plasma coupling factor 6 (CF6) in endothelial cells via protein kinase C (PKC) and p38 MAPK pathways. Insulin treatment counteracted this effect, suggesting a novel mechanism in diabetes mellitus.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Vascular Biology

Background:

  • Plasma coupling factor 6 (CF6) is a novel vasoactive peptide.
  • Elevated CF6 levels are observed in patients with diabetes mellitus.
  • The underlying mechanism for CF6 elevation in diabetes remains unclear.

Purpose of the Study:

  • To investigate the mechanism of CF6 protein release in human umbilical vein endothelial cells (HUVECs).
  • To determine the effect of high glucose on CF6 expression and secretion.
  • To elucidate the signaling pathways involved in high glucose-induced CF6 release.

Main Methods:

  • HUVECs were incubated with varying concentrations and durations of high glucose.
  • Osmolarity effects were controlled for.
  • Protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK) inhibitors were used.
  • Insulin treatment was applied to assess its effect on CF6 production.

Main Results:

  • High glucose significantly enhanced CF6 expression and secretion in HUVECs in a time- and concentration-dependent manner.
  • This effect was independent of increased osmolarity.
  • Inhibition of PKC and p38 MAPK suppressed high glucose-mediated CF6 release by -45% and -30%, respectively.
  • Insulin treatment antagonized high glucose-induced CF6 production.

Conclusions:

  • High glucose increases CF6 expression and secretion in endothelial cells.
  • The mechanism involves the activation of PKC and p38 MAPK signaling pathways.
  • These findings suggest a potential role for CF6 in the pathophysiology of diabetes mellitus.

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