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Mechanisms of putative IGF-I receptor resistance in active acromegaly

机译:强定IGF-I受体抗性机制活性临床

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摘要

Acromegaly is a disease characterized by overproduction of growth hormone (GH). As a consequence of excessive GH secretion, circulating insulin-like growth factor-I (IGF-I) is elevated in active (untreated) acromegaly. IGF-I is often used as a marker of disease activity and growth hormone status in acromegaly. Although IGF-I can directly improve insulin sensitivity and glucose uptake in muscles, the excessive GH secretion in active acromegaly frequently leads to insulin resistance, glucose intolerance and even diabetes. In this review evidence will be discussed that in active acromegaly chronically elevated IGF-I, insulin and soluble Klotho (S-Klotho) levels play a pathophysiological role in the development of IGF-I receptor (IGF-IR) resistance. It is postulated that as soon as circulating IGF-I, insulin and S-Klotho rise above a certain level the IGF-IR becomes relatively resistant to actions of IGF-I. The development of a degree of IGF-IR resistance for metabolic actions may help to explain why in active acromegaly diabetogenic effects of GH predominate and are not completely counteracted and neutralized by elevated circulating levels of IGF-I. Further studies are necessary in order to support this hypothesis.
机译:AcromeGaly是一种疾病,其特征在于生长激素(GH)的过度生产。由于GH分泌过多,循环胰岛素样生长因子-1(IGF-1)在活性(未处理的)焦达谷物中升高。 IGF-I经常被用作患者患者活性和生长激素地位的标志物。虽然IGF-I可以直接改善肌肉敏感性和葡萄糖摄取,但活性棘手症中的过量GH分泌经常导致胰岛素抵抗,葡萄糖不耐受甚至糖尿病。在本次审查中,将讨论中,在活性终止性慢性升高的IGF-I,胰岛素和可溶性Klotho(S-Klotho)水平在IGF-I受体(IGF-IR)抗性的发育中起到病理生理作用。假设它一旦循环IGF-I,胰岛素和S-Klotho高于一定水平,IGF-IR变得相对抗IGF-1的作用。对代谢作用的IGF-IR抗性程度的发展可能有助于解释为什么在GH的活性致喉糖尿病效果中,通过升高的IGF-I升高的循环水平并不完全抵消和中和。进一步的研究是为了支持这一假设。

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