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Arch Hellen Med, 26(1), January-February 2009, 42-50


The role of ghrelin on glucose homeostasis

2nd Department of Propedeutic Surgery, University of Athens, “Laiko” Hospital, Athens, Greece

Ghrelin, a newly identified acylated 28-amino-acid peptide and an endogenous ligand of the growth hormone secretagogue type 1a receptor (GHS-R1a), is produced mainly in the stomach, but is also secreted in low levels by the hypothalamus and by many other peripheral tissues. Ghrelin is best known for its hypothalamic actions on growth hormone- releasing hormone neurons and neuropeptide Y/agouti-related peptide neurons. Although ghrelin affects multiple systems and many organs, only currently the complexity of its functions has been realized in mammals and especially in humans. Ghrelin regulates food intake and body weight, and GHS-R1a that is expressed at lower levels in the brain, including the hypothalamic neurons, regulates feeding behavior and glucose sensing. A reciprocal relationship exists between ghrelin and insulin, suggesting that ghrelin regulates glucose homeostasis. Ablation of ghrelin in mice increases glucose-induced insulin secretion and improves peripheral insulin sensitivity. Recent reports suggest that most of the actions of ghrelin could contribute to the metabolic syndrome. The ghrelin signaling system is, therefore, a promising target for the development of new drugs for the treatment of diabetes. Agents that block the ghrelin signaling system might be especially useful. This review focuses on the newly emerging role of ghrelin in glucose homeostasis and insulin secretion, and on the exploration of whether it may be a potential therapeutic target for diabetes mellitus; if so, it is possible that the high rates of morbidity and mortality of diabetes mellitus patients could be diminished.

Key words: Diabetes, Ghrelin, Growth hormone secretagogues (GHSs), Glucose homeostasis, Insulin secretion.

© Archives of Hellenic Medicine