Modulation of retinal endothelial cell behaviour by insulin-like growth factor I and somatostatin analogues: Implications for diabetic retinopathy

Sylvia H. Wilson, Margaret I. Davis, Sergio Caballero, Maria B. Grant

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Evidence suggests the involvement of growth hormone (GH), insulin-like growth factor I (IGF-I) and somatostatin in the pathology associated with diabetic retinopathy. We examined the effect of IGF-I on human retinal endothelial cell (HREC) survival following high glucose exposure and serum starvation, examined the signalling pathways mediating the protective effect of IGF-I on HREC, and characterized somatostatin receptor-induced retinal endothelial cell death. IGF-I (10 ng/ml) protected HREC from apoptosis induced by high glucose and serum starvation. Wortmannin, a specific inhibitor of phosphotidylinositol-3-kinase, blocks the ability of IGF-I to protect HREC from apoptosis. Incubation of HREC in serum-free medium caused a time-dependent increase in c-Jun N-terminal kinase (JNK) activity, and continuous culture of HREC in the presence of IGF-I or vascular endothelial growth factor (VEGF) prevented JNK activation and arrested apoptosis. Activation of tyrosine kinase receptors results in extracellular signal-related kinase (ERK) activation and activation of ERK is required for proliferation. Both IGF-I and VEGF produced a time- and concentration-dependent increase in the activation of ERK. Type 2 and type 3 somatostatin receptors have been implicated in cell-cycle arrest and apoptosis. Activation of the type 3 receptor in HREC resulted in cell death. These studies suggest that IGF-I is critical for HREC survival, and that somatostatin analogues acting through the type 3 receptor have direct effects on retinal endothelial cells. Furthermore, it appears that the therapeutic efficacy of somatostatin analogues lies not only in systemic inhibition of GH, but also in modulating local growth factor effects.

Original languageEnglish (US)
Pages (from-to)S53-S59
JournalGrowth Hormone and IGF Research
Volume11
Issue numberSUPPL. 1
DOIs
StatePublished - Jan 1 2001

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Keywords

  • Cell behaviour
  • Diabetic retinopathy
  • Endothelial cells
  • Insulin-like growth factor I
  • Retina
  • Somatostatin analogues

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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