Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes.
Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes.
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DOI：
10.1016/j.ecl.2012.04.017
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发表时间：
2012-06
影响因子：
4.5
通讯作者：
Clemmons DR
中科院分区：
文献类型：
--
作者：
Clemmons DR
胰岛素样生长因子-I (IGF-I) 与胰岛素密切相关，但具有不同的代谢作用。 IGF-I 是肌肉中蛋白质合成的重要刺激剂，但它也刺激游离脂肪酸的利用。 IGF-I 影响新陈代谢的重要间接作用包括抑制生长激素分泌和在超生理浓度下抑制胰岛素分泌。 IGF-I 作用受 IGF 结合蛋白调节，在肥胖和代谢综合征中，IGF 结合蛋白分泌存在严重失调，导致游离 IGF-I 和 IGF-I 作用浓度的变化。在 1 型糖尿病中，IGF-I 合成明显受损，而在 2 型糖尿病中，IGF-I 作用发生多种变化，包括在某些靶组织中对其促有丝分裂作用敏感。对具有极端胰岛素抵抗的患者施用IGF-I可改善血糖控制，并且IGF-I已被证明与降低1型和2型糖尿病的血糖并增强胰岛素敏感性有关。然而，糖尿病患者对 IGF-I 的副作用刺激也非常敏感，这极大地限制了其作为降血糖药的用途。 IGF-I 协调连接生长激素和胰岛素的作用，并对中间代谢产生直接影响。
Insulin-like growth factor-I (IGF-I) is closely related to insulin but has distinct metabolic actions. IGF-I is an important stimulant of protein synthesis in muscle but it also stimulates free fatty acid utilization. Important indirect effects of IGF-I that influence metabolism include suppression of growth hormone secretion and at supraphysiologic concentrations suppression of insulin secretion. IGF-I actions are regulated by IGF binding proteins and in obesity and metabolic syndrome there is major dysregulation of IGF binding protein secretion resulting in alterations in the concentration of free IGF-I and IGF-I actions. In type 1 diabetes, IGF-I synthesis is markedly impaired and in type 2 diabetes multiple changes occur in IGF-I actions including sensitization to its mitogenic actions in some target tissues. Administration of IGF-I to patients with extreme insulin resistance results in improvement in glycemic control and IGF-I has been shown to be associated with lowering glucose and enhancing insulin sensitivity in both type 1 and type 2 diabetes. However diabetics are also quite sensitive to stimulation of side effects in response to IGF-I and this has greatly limited its usefulness as a hypoglycemic agent. IGF-I coordinately links growth hormone and insulin actions as well as having direct effects on intermediary metabolism.