Department of Internal Medicine, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
Peptides. 2011 Nov;32(11):2309-18. doi: 10.1016/j.peptides.2011.03.001. Epub 2011 Mar 21.
Ghrelin plays an important physiological role in modulating GH secretion, insulin secretion and glucose metabolism. Ghrelin has direct effects on pancreatic islet function. Also, ghrelin is part of a mechanism that integrates the physiological response to fasting. However, pharmacologic studies indicate the important obesogenic/diabetogenic properties of ghrelin. This is very likely of physiological relevance, deriving from a requirement to protect against seasonal periods of food scarcity by building energy reserves, predominantly in the form of fat. Available data indicate the potential of ghrelin blockade as a means to prevent its diabetogenic effects. Several studies indicate a negative correlation between ghrelin levels and the incidence of type 2 diabetes and insulin resistance. However, it is unclear if low ghrelin levels are a risk factor or a compensatory response. Direct antagonism of the receptor does not always have the desired effects, however, since it can cause increased body weight gain. Pharmacological suppression of the ghrelin/des-acyl ghrelin ratio by treatment with des-acyl ghrelin may also be a viable alternative approach which appears to improve insulin sensitivity. A promising recently developed approach appears to be through the blockade of GOAT activity, although the longer term effects of this treatment remain to be investigated.
生长激素释放肽在调节 GH 分泌、胰岛素分泌和葡萄糖代谢方面发挥着重要的生理作用。生长激素释放肽对胰岛功能有直接影响。此外，生长激素释放肽是一种整合饥饿生理反应的机制的一部分。然而，药理学研究表明生长激素释放肽具有重要的致肥胖/致糖尿病特性。这很可能具有生理相关性，源于通过建立能量储备（主要以脂肪的形式）来保护身体免受季节性食物匮乏的需求。现有数据表明，生长激素释放肽阻断可能是预防其致糖尿病作用的一种手段。几项研究表明，生长激素释放肽水平与 2 型糖尿病和胰岛素抵抗的发生率呈负相关。然而，目前尚不清楚低水平的生长激素释放肽是危险因素还是代偿性反应。然而，直接拮抗受体并不总是能达到预期的效果，因为它会导致体重增加。通过用去酰基生长激素释放肽治疗来抑制生长激素/去酰基生长激素释放肽的比值，也可能是一种可行的替代方法，似乎可以改善胰岛素敏感性。一种有前途的新方法似乎是通过阻断 GOAT 活性，尽管这种治疗的长期效果仍有待研究。
