We investigated the metabolic actions of
ghrelin in humans by examining the effects of acute administration of acylated
ghrelin, unacylated
ghrelin, and the combination in eight adult-onset GH-deficient patients. We followed
glucose,
insulin, and
free fatty acid concentrations before and after lunch and with or without the presence of GH in the circulation. We found that acylated
ghrelin, which is rapidly cleared from the circulation, induced a rapid rise in
glucose and
insulin levels. Unacylated
ghrelin, however, prevented the acylated
ghrelin-induced rise in
insulin and
glucose when it was coadministered with acylated
ghrelin. Surprisingly, the injection of acylated
ghrelin induced an acute increase in unacylated
ghrelin and therefore total
ghrelin levels. Finally, acylated
ghrelin decreased
insulin sensitivity up to the end of a period of 6 h after administration. This decrease in
insulin sensitivity was prevented by coinjection of unacylated
ghrelin. This combined administration of acylated and unacylated
ghrelin even significantly improved
insulin sensitivity, compared with placebo, for at least 6 h, which warrants studies to investigate the long-term efficacy of this combination in the treatment of disorders with disturbed
insulin sensitivity.