Endocrine Abstracts

Endothelial dysfunction is thought to be a major cause of vascular complications in diabetes. Our research shows that obestatin, a 23-aminoacid amidated peptide recently identified as a product of the ghrelin gene, inhibited high glucose-induced apoptosis in cultured bovine aortic endothelial cells (BAEC). Exposure to high glucose concentration (30 mM) for 72 h caused a significant increase in apoptosis, as evaluated by Hoechst staining, but co-treatment of rat obestatin (from 10⁻¹¹ to 10⁻⁷ nM) eliminated in a dose–dependent manner high glucose-induced apoptosis in BAEC. Obestatin also protected endothelial cells from high glucose by reducing reactive oxygen species (ROS) production. Blockade of adenylyl cyclase and cAMP-dependent protein kinase A signalling prevented the inhibitory effect of obestatin on ROS production. Obestatin also activated phosphatidyl inositol 3-kinase (PI3K/Akt) and ERK1/2 pathway, whereas PI3K and ERK inhibitors counteracted the obestatin anti-apoptotic effect. Finally, saturation binding studies with radioiodinated [¹²⁵I]-obestatin recognized high-affinity (K_d=0.5 nM) specific binding sites in the BAEC cell line, suggesting that these sites may be involved in the cytoprotective effect of the peptide. In conclusion, the results of our study demonstrate, for the first time, that obestatin inhibits both high glucose-induced apoptosis and ROS production in endothelial cells and suggest that this peptide may have potential in preventing vascular complications in diabetic patients.