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Tong, J.* ; Davis, H.W.* ; Summer, S.* ; Benoit, S.C.* ; Haque, A.* ; Bidlingmaier, M.* ; Tschöp, M.H. ; D'Alessio, D.*

Acute administration of unacylated ghrelin has no effect on basal or stimulated insulin secretion in healthy humans.

Diabetes 63, 2309-2319 (2014)

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Unacylated ghrelin (UAG) is the predominant ghrelin isoform in the circulation. Despite its inability to activate the classical ghrelin receptor, preclinical studies suggest that UAG may promote β-cell function. We hypothesized that UAG would oppose the effects of acylated ghrelin (AG) on insulin secretion and glucose tolerance. AG (1 µg/kg/h), UAG (4 µg/kg/h), combined AG+UAG, or saline were infused to 17 healthy subjects (9 M/8 F) on 4 occasions in randomized order. Ghrelin was infused for 30 min to achieve steady-state levels and continued through a 3-h IV glucose tolerance test. The acute insulin response to glucose (AIRg), insulin sensitivity index (SI), disposition index (DI), and IV glucose tolerance (kg) were compared for each subject during the 4 infusions. AG infusion raised fasting glucose levels but had no effect on fasting plasma insulin. Compared to the saline control both AG and AG+UAG decreased AIRg, but UAG alone had no effect. SI did not differ among the treatments. AG, but not UAG, reduced DI and kg and increased plasma growth hormone. UAG did not alter growth hormone, cortisol, glucagon or free fatty acid levels. UAG selectively decreased glucose and fructose consumption compared to the other treatments. In contrast to previous reports, acute administration of UAG does not have independent effects on glucose tolerance or β-cell function, and neither augments nor antagonizes the effects of AG.

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