Acute Administration of Unacylated Ghrelin Has No Effect on Basal or Stimulated Insulin Secretion in Healthy Humans

作者：Tong Jenny^*; Davis Harold W; Summer Suzanne; Benoit Stephen C; Haque Ahrar; Bidlingmaier Martin; Tschoep Matthias H; D' Alessio David

来源：Diabetes, 2014, 63(7): 2309-2319.

DOI：10.2337/db13-1598

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 beta-cell function. We hypothesized that UAG would oppose the effects of acylated ghrelin (AG) on insulin secretion and glucose tolerance. AG (1 mu g/kg/h), UAG (4 mu g/kg/h), combined AG+UAG, or saline were infused to 17 healthy subjects (9 men and 8 women) on four occasions in randomized order. Ghrelin was infused for 30 min to achieve steady-state levels and continued through a 3-h intravenous glucose tolerance test. The acute insulin response to glucose (AIRg), insulin sensitivity index (S-I), disposition index (DI), and intravenous glucose tolerance (k(g)) were compared for each subject during the four infusions. AG infusion raised fasting glucose levels but had no effect on fasting plasma insulin. Compared with the saline control, AG and AG+UAG both decreased AIRg, but UAG alone had no effect. S-I did not differ among the treatments. AG, but not UAG, reduced DI and k(g) 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 with the other treatments. In contrast to previous reports, acute administration of UAG does not have independent effects on glucose tolerance or beta-cell function and neither augments nor antagonizes the effects of AG.

• 出版日期2014-7