Endocrine Abstracts

Background: Des-acyl ghrelin (Des-G) is an isoform of ghrelin without the n-octanoyl modification at Ser3 present in this peptide. It is mainly produced in endocrine cells located in the stomach, in the mucosal layer of the fundus, and it is secreted into bloodstream where it circulates in higher amounts than ghrelin (2:1).

Although Des-G was previously thought of as a non-functional peptide, since it does not activate GHS-R1a, recent studies have shown that it is able to share with ghrelin antiproliferative effects on breast and prostate cancer cell lines, and can stimulate adipogenesis and regulate glucose secretion in hepatocytes.

The aim of our study was to investigate if Des-G could also regulate cardiomyocytes viability and metabolism.

Materials and methods: Using MTT assay we demonstrate that Des-G did not change HL-1 cardiomyocytes metabolic activity. However, pre-treatment with Des-G (0.1 μM) for 12 hours prevented the apoptosis induced by treatment with cytosine arabinoside (AraC, 0.1 μM) in HL-1 cells. Des-G (1 and 3 μM), increased significantly the fatty acid uptake (assayed by Bodipy) in HL-1 cardiomyocytes while ghrelin inhibited this stimulatory effect of Des-G. Ghrelin (30 min, 3 μM) also inhibited 2-deoxi-D-[³H]glucose uptake induced by insulin (1 hour, 100 nM) in HL-1 cardiomyocytes while Des-G lacked this effect. Furthermore Des-G (in equimolar doses) was able to prevent the inhibitory effect of ghrelin on insulin-induced glucose uptake.

Conclusions: Des-G, as ghrelin does, has a protective effect against the apoptosis induced by AraC in HL-1 cells. In terms of cardiomyocytes glucose and lipid metabolism Des-G counteracts the negative effect of ghrelin in insulin-induced glucose uptake, while it stimulates long chain fatty acid uptake in this cell type.