JCEM：生理浓度的生长激素释放肽输注降低胰岛素分泌

在人类，输注超生理剂量的生长激素释放肽抑制葡萄糖刺激的胰岛素分泌，降低胰岛素敏感性，并降低葡萄糖耐量。为了确定在健康男性和女性，小剂量的生长激素释放肽对胰岛素分泌和胰岛素敏感性的影响，来自美国辛辛那提大学医学部的Jenny Tong教授及其团队进行了一项研究，该研究发现生理状态的生长激素释放肽输注降低胰岛素分泌，不影响胰岛素敏感性。该研究结果在线发表在2013年4月15日的美国《临床内分泌代谢杂志》上。
该研究中，在16例健康受试者按随机顺序，在3个单独的场合，输注酰基化生长激素释放肽（0.2和0.6nmol kg-1 hr-1）或生理盐水225分钟。进行静脉葡萄糖耐量试验，胰岛素敏感指数（S1）来源于最小模型。用葡萄糖的急性胰岛素反应（AIRg）和处置指数（DI）的计算判断胰岛素分泌，如AIRg×S1。
该研究结果表明，在0.2和0.6nmol kg-1 hr-1输注生长激素释放肽时，稳态血浆总生长激素释放肽水平在空腹浓度上提高2.2和6.1倍。两种生长激素释放肽剂量都不改变空腹血浆胰岛素，血糖或S1，但两种剂量都比生理盐水对照组降低胰岛素分泌，无论是计算AIRg（分别为384±75和354±65对520±110pM·min；P＜0.01），还是DI（分别为2238±421和2067±396对3339±705；P＜0.02）。大剂量生长激素释放肽输注也降低葡萄糖耐量。
该研究发现，生长激素释放肽的输注发生在生理状态水平，如禁食时，降低胰岛素分泌，不影响胰岛素敏感性。这些发现与内源性生长激素释放肽在调节胰岛素分泌中的作用相一致，提示拮抗生长激素释放肽可以改善β细胞功能。
与胰岛素相关的拓展阅读：

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Physiologic concentrations of exogenously infused ghrelin reduces insulin secretion without affecting insulin sensitivity in healthy humans.
Abstract
Infusion of ghrelin to supraphysiologic levels inhibits glucose-stimulated insulin secretion, reduces insulin sensitivity and worsens glucose tolerance in humans.Objective:To determine the effects of lower doses of ghrelin on insulin secretion and insulin sensitivity in healthy men and women.Methods:Acyl ghrelin (0.2 and 0.6 nmol kg-1 hr-1) or saline was infused for 225 min in 16 healthy subjects on 3 separate occasions in randomized order. An IV glucose tolerance test was performed and the insulin sensitivity index (SI) derived from the minimal model. Insulin secretion was measured as the acute insulin response to glucose (AIRg) and the disposition index (DI) computed as AIRg x SI.Results:Ghrelin infusions at 0.2 and 0.6 nmol kg-1 hr-1 raised steady-state plasma total ghrelin levels 2.2 and 6.1-fold above fasting concentrations. Neither dose of ghrelin altered fasting plasma insulin, glucose, or SI, but both doses reduced insulin secretion compared to the saline control, computed either as AIRg (384 ± 75 and 354 ± 65 vs. 520 ± 110 pM·min, respectively, mean ± SEM; p < 0.01 for both low-and high-dose vs. saline) or DI (2238 ± 421 and 2067 ± 396 vs. 3339 ± 705, respectively; p < 0.02 for both comparisons). The high-dose ghrelin infusion also decreased glucose tolerance.Conclusions:Ghrelin infused to levels occurring in physiologic states such as starvation decreases insulin secretion without affecting insulin sensitivity. These findings are consistent with a role for endogenous ghrelin in the regulation of insulin secretion, and suggest that ghrelin antagonism could improve β-cell function.