Pinitol in Human Nutrition

项目描述（由申请人提供）：该项目的长期目标是通过更好地了解新认识的膳食成分pinitol，改善多囊卵巢综合征、高甘油三酯血症、代谢综合征和2型糖尿病患者高胰岛素血症的代谢并发症。Pinitol （3- o-甲基- d -chiro-inositol）是一种与肌醇相关的糖，存在于哺乳动物中介分子中。Pinitol及其去甲基化产物d -chiro-肌醇已被鉴定为具有小分子量生物活性的肌醇聚糖，具有几种不同的信号通路，包括一些与胰岛素作用有关的信号通路。研究发现，在高胰岛素血症患者中，用d -氨基肌醇或蒎醇治疗可以降低胰岛素水平、降低血红蛋白Alc、降低血清睾酮水平和降低血清甘油三酯水平。我们的实验室已经确定，虽然大多数食物中的肌醇含量很低，但它是豆类和柑橘类水果的主要成分，而饮食是人体肌醇水平的主要贡献者。人体内的肌醇被酶转化为d -氨基肌醇。我们开发了一种使用气相色谱/负离子质谱法的高灵敏度肌醇测定方法，可以测量血清和尿液中的皮摩尔量。拟议的工作将验证这样一种假设，即在人类受试者中，膳食中添加匹尼醇会提高血浆匹尼醇和d -氨基肌醇水平，并降低血浆胰岛素、血浆游离脂肪酸和甘油三酯。这些肌醇的动力学将使用专门制备的氘化示踪剂进行研究。这项工作将为高胰岛素血症患者提供关于匹尼醇消耗、代谢、动力学和代谢效应的基本信息。从长远来看，有可能通过饮食建议或从食物废物流中回收蒎醇来改善人类的高胰岛素状态。

DESCRIPTION (provided by applicant): The long term goal of this project is to improve the metabolic complications of hyperinsulinemia in patients with polycystic ovary syndrome, hypertriglyceridemia, metabolic syndrome and type 2 diabetes mellitus by better understanding the newly-recognized dietary component pinitol. Pinitol (3-O-methyl-D-chiro-inositol) is a sugar related to myo-inositol, which is found in mammalian mediator molecules. Pinitol and its demethylated product D-chiro-inositol have been identified in small molecular weight bioactive inositol glycans from several different signaling pathways, including some related to insulin action. Treatment of patients with D-chiro-inositol or pinitol has been found to reduce insulin levels, lower hemoglobin Alc, lower elevated serum testosterone and reduce serum triglycerides in hyperinsulinemic patients. Our laboratory has established that pinitol, while very low in most foods, is a major component of legumes and citrus fruits, and that diet is a major contributor to body inositol levels. Pinitol is enzymatically converted to D-chiro-inositol in humans. We have developed a highly-sensitive inositol assay using gas chromatography/negative ion mass spectrometry that allows measurement of picomole amounts in serum and urine. The proposed work will test the hypothesis that, in human subjects, dietary pinitol administration elevates plasma pinitol and D-chiro-inositol levels and reduces plasma insulin, plasma free fatty acids and triglycerides. The kinetics of these inositols will be studied using specially-prepared deuterated tracers. This work will provide basic information about pinitol consumption, metabolism, kinetics and metabolic effects in hyperinsulinemic subjects. In the long term it may be possible to improve human hyperinsulinemic states by dietary recommendations or by recovering pinitol from food waste streams.