Physiological roles of des-acyl ghrelin

Ghrelin circulates into two different forms: (1) acylated ghrelin (AG) which holds an n -octanoic acid at its third serine residue, and (2) des-acyl ghrelin (DAG). AG, but not DAG, binds the GH secretagogue type 1a receptor (GHS-R1a) and stimulates secretion of GH and other pituitary hormones. Accumulating evidence indicate that both AG and DAG have non-GHS-R1a-mediated biological activities and particularly exert a significant role in the fine-tuning of insulin secretion and glucose metabolism, sometimes acting as agonists others as antagonists. DAG promotes insulin secretion from b -cell lines and enhances the portal insulin response following an intravenous glucose tolerance test in rats. In addition, DAG has been shown to inhibit in vitro hepatic glucose output, suggesting that at least part of the beneficial effect on glucose could also be secondary to an insulin-independent mechanism. Finally, recent results suggest that DAG has also proliferative and protective effects on b -cells. Transgenic mice over-expressing DAG display reduced fat mass and blood triglycerides. Also, the coadministration of AG and DAG reduces plasma FFA in GHD patients. Finally, results of recent preliminary experiments on circulating angiogenic cells (CAC) suggest that DAG may beneficially impact the vascular remodeling process, which is known to be impaired in type 2 diabetes patients.