Ghrelin and new metabolic frontiers

Background: A growing body of literature has profiled the complex identities and interactions of ghrelin analogues and their known and unknown receptors, which constitute the ghrelin system. In humans, acylated ghrelin (AG) induces a rapid rise in glucose and insulin levels. However, coadministration of unacylated ghrelin (UAG) counteracts this effect. Accumulating data support the existence of a specific receptor for UAG in addition to the corticotropin-releasing factor 2 receptor and the growth hormone secretagogue type 1a receptor. Preclinically, mice that overexpress UAG exhibit decreased body weight, food intake, free fatty acid levels and fat pad mass weight and moderately decreased linear growth. In humans, intravenous infusion of UAG in normal subjects enhances the early insulin response to meals, improves glucose metabolism and insulin sensitivity and inhibits lipolysis. Conclusions: AG and UAG play an important regulatory role in metabolism.

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