Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans.
Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans.
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DOI：
10.2337/db10-0504
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发表时间：
2010-09
期刊：
影响因子：
7.7
通讯作者：
D'Alessio D
中科院分区：
文献类型：
--
作者：
Tong J;Prigeon RL;Davis HW;Bidlingmaier M;Kahn SE;Cummings DE;Tschöp MH;D'Alessio D
促食欲肠道激素胃饥饿素及其受体存在于胰岛中。尽管胃饥饿素在啮齿动物中会减少胰岛素分泌，但其对人类胰岛素分泌的影响尚未确定。本研究的目的是验证循环胃饥饿素在健康受试者中抑制葡萄糖刺激的胰岛素分泌这一假设。
在12名健康患者（8名男性/4名女性）中，以平衡的方式在4个不同场合分别输注胃饥饿素（0.3、0.9和1.5 nmol/kg/h）或生理盐水超过65分钟。在稳定的血浆胃饥饿素水平期间进行静脉葡萄糖耐量试验。根据葡萄糖推注后2至10分钟之间的血浆胰岛素浓度计算对静脉葡萄糖的急性胰岛素反应（AIRg）。静脉葡萄糖耐量以10至30分钟的葡萄糖消失常数（Kg）来衡量。
三种胃饥饿素输注分别使血浆总胃饥饿素浓度升高至空腹水平的4倍、15倍和23倍。胃饥饿素输注未改变空腹血浆胰岛素或葡萄糖，但与生理盐水相比，0.3、0.9和1.5 nmol/kg/h的剂量显著降低了AIRg（分别为2152 ± 448比1478 ± 2889、1419 ± 275和1120 ± 174 pmol/L）以及Kg（仅0.3和1.5 nmol/kg/h剂量）（所有P < 0.05）。胃饥饿素输注显著提高了血浆生长激素和血清皮质醇浓度（两者P < 0.001），但对胰高血糖素、肾上腺素或去甲肾上腺素水平无影响（分别为P = 0.44、0.74和0.48）。
这是一项有力的概念验证研究，表明外源性胃饥饿素会减少健康人葡萄糖刺激的胰岛素分泌和葡萄糖消失。我们的研究结果提出了内源性胃饥饿素在生理性胰岛素分泌中起作用的可能性，以及胃饥饿素拮抗剂可能改善β细胞功能。
The orexigenic gut hormone ghrelin and its receptor are present in pancreatic islets. Although ghrelin reduces insulin secretion in rodents, its effect on insulin secretion in humans has not been established. The goal of this study was to test the hypothesis that circulating ghrelin suppresses glucose-stimulated insulin secretion in healthy subjects. Ghrelin (0.3, 0.9 and 1.5 nmol/kg/h) or saline was infused for more than 65 min in 12 healthy patients (8 male/4 female) on 4 separate occasions in a counterbalanced fashion. An intravenous glucose tolerance test was performed during steady state plasma ghrelin levels. The acute insulin response to intravenous glucose (AIRg) was calculated from plasma insulin concentrations between 2 and 10 min after the glucose bolus. Intravenous glucose tolerance was measured as the glucose disappearance constant (Kg) from 10 to 30 min. The three ghrelin infusions raised plasma total ghrelin concentrations to 4-, 15-, and 23-fold above the fasting level, respectively. Ghrelin infusion did not alter fasting plasma insulin or glucose, but compared with saline, the 0.3, 0.9, and 1.5 nmol/kg/h doses decreased AIRg (2,152 ± 448 vs. 1,478 ± 2,889, 1,419 ± 275, and 1,120 ± 174 pmol/l) and Kg (0.3 and 1.5 nmol/kg/h doses only) significantly (P < 0.05 for all). Ghrelin infusion raised plasma growth hormone and serum cortisol concentrations significantly (P < 0.001 for both), but had no effect on glucagon, epinephrine, or norepinephrine levels (P = 0.44, 0.74, and 0.48, respectively). This is a robust proof-of-concept study showing that exogenous ghrelin reduces glucose-stimulated insulin secretion and glucose disappearance in healthy humans. Our findings raise the possibility that endogenous ghrelin has a role in physiologic insulin secretion, and that ghrelin antagonists could improve β-cell function.
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