d -氨基肌醇在胰岛素作用中的功能作用及其在胰岛素抵抗中的缺陷

J. Larner,
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引用次数: 252

摘要

在这篇综述中,我们讨论了d -氨基肌醇的生物学意义,它最初被认为是细胞内胰岛素作用的一种介质,作为一种假定的介质,它加速了糖原合成酶和丙酮酸脱氢酶的去磷酸化,这些酶是非氧化性和氧化性葡萄糖处理的限速酶。早期研究表明,尿量减少与胰岛素抵抗程度呈线性关系。当对2型糖尿病患者的组织内容物(包括肌肉)进行分析时,他们表现出更普遍的身体缺陷。给糖尿病大鼠、恒河猴和现在给人注射d -氨基肌醇加速了葡萄糖的处理,并使胰岛素的作用变得敏感。GK型2型糖尿病大鼠胰岛素敏感组织肌肌醇向手性肌醇的外显体化在体内存在缺陷。因此,给药的d -手性肌醇可以绕过与胰岛素抵抗相关的肌醇向d -手性肌醇的正常外显异构化缺陷,并至少部分恢复胰岛素敏感性和葡萄糖处理。
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D-Chiro-Inositol – Its Functional Role in Insulin Action and its Deficit in Insulin Resistance
In this review we discuss the biological significance of D-chiro-inositol, originally discovered as a component of a putative mediator of intracellular insulin action, where as a putative mediator, it accelerates the dephosphorylation of glycogen synthase and pyruvate dehydrogenase, rate limiting enzymes of non-oxidative and oxidative glucose disposal. Early studies demonstrated a linear relationship between its decreased urinary excretion and the degree of insulin resistance present. When tissue contents, including muscle, of type 2 diabetic subjects were assayed, they demonstrated a more general body deficiency. Administration of D-chiro-inositol to diabetic rats, Rhesus monkeys and now to humans accelerated glucose disposal and sensitized insulin action. A defect in vivo in the epimerization of myoinositol to chiro-inositol in insulin sensitive tissues of the GK type 2 diabetic rat has been elucidated. Thus, administered D-chiro-inositol may act to bypass a defective normal epimerization of myo-inositol to D-chiro-inositol associated with insulin resistance and act to at least partially restore insulin sensitivity and glucose disposal.
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