Pinitol in Human Nutrition

描述（由申请人提供）：本项目的长期目标是通过更好地了解新认识的膳食成分松醇，改善多囊卵巢综合征、高胰岛素血症、代谢综合征和2型糖尿病患者的高胰岛素血症代谢并发症。松醇（3-O-甲基-D-手性-肌醇）是与肌醇相关的糖，其在哺乳动物介质分子中发现。松醇及其去甲基化产物D-手性肌醇已在来自几种不同信号通路的小分子量生物活性肌醇聚糖中被鉴定，包括一些与胰岛素作用相关的信号通路。已发现用D-手性肌醇或松醇治疗患者可降低高胰岛素血症患者的胰岛素水平、降低血红蛋白Alc、降低升高的血清睾酮和降低血清甘油三酯。我们的实验室已经确定，松醇，而在大多数食物中非常低，是豆类和柑橘类水果的主要成分，饮食是身体肌醇水平的主要贡献者。在人体内，松醇被酶促转化为D-手性肌醇。我们开发了一种高灵敏度的肌醇测定方法，使用气相色谱/负离子质谱法，可以测量血清和尿液中的皮摩尔量。拟议的工作将测试的假设，在人类受试者中，饮食松醇管理提高血浆松醇和D-手性肌醇水平，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代示踪剂进行研究。这项工作将提供有关高胰岛素血症受试者的松醇消耗，代谢，动力学和代谢效应的基本信息。从长远来看，通过饮食建议或从食物废物流中回收松醇，有可能改善人类高胰岛素血症状态。

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.