VANADIUM SALTS AND CARBOHYDRATE METABOLISM

钒盐和碳水化合物代谢

• 批准号: 3248697
• 负责人: LUCIANO ROSSETTI
• 金额: $ 25.48万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3248697
• 关键词: blood glucose; carbohydrate metabolism; clinical trials; diabetes mellitus; diabetes mellitus therapy; drug screening /evaluation; glucose tolerance test; human subject; human therapy evaluation; hypoglycemic agents; insulin sensitivity /resistance; vanadium

Insulin resistance is a common characteristic of the diabetic state and of several other pathological conditions, such as hypertension and obesity. Over the last several years, numerous reports have demonstrated the in vitro and in vivo insulin-like activity of vanadate salts. Particularly, vanadate has been shown to stimulate glucose uptake and glycogen synthase activity in hepatocytes, adipocytes, diaphragm and skeletal muscle. Recently, we have demonstrated that the oral administration of vanadate salts improves glucose tolerance and completely normalizes insulin- mediated glucose uptake in diabetic animals, primarily through the stimulation of skeletal muscle glycogen synthesis. These and other previous observations support the hypothesis that this trace element can potentiate insulin action at the cellular level and that trace element therapy, either alone or in combination, may prove effective in the treatment of human diabetes mellitus. Insulin maintains glucose homeostasis by two major mechanisms: a) suppression of hepatic glucose production; b) stimulation of peripheral (muscle) glucose uptake. Once glucose is transported into the cell, it is phosphorylated to glucose 6- phosphate (G-6-P) and enters one of two major pathways, glycogen synthesis and glycolysis. In turn, glycolysis leads either to lactate formation or pyruvate oxidation in the Krebs cycle Recently, techniques have been developed to measure in vivo the rates of insulin-mediated glucose metabolism in humans. Thus, in the present study, we propose to examine the effect of the oral administration of vanadate on glucose tolerance, insulin-mediated glucose disposal, glucose oxidation, glycolysis and glycogen synthesis in healthy volunteers, IDDM and NIDDM subjects. This will be a placebo-controlled trial to obtain preliminary information regarding the short-term efficacy and safety of this trace element in human subjects.

胰岛素抵抗是糖尿病状态和 其他几种病理状况，例如高血压和肥胖症。 在过去的几年中，许多报告证明了 钒酸盐的体外和体内胰岛素样活性。特别， 钒酸盐已显示可刺激葡萄糖摄取和糖原合酶 肝细胞，脂肪细胞，隔膜和骨骼肌的活性。 最近，我们已经证明了口服钒酸盐的口服给药 盐可提高葡萄糖耐受性，并完全使胰岛素正常化 - 糖尿病动物中介导的葡萄糖摄取，主要是通过 刺激骨骼肌糖原合成。这些和其他 以前的观察结果支持以下假设 在细胞水平上增强胰岛素作用，该痕量元素 单独或合并的治疗可能在 治疗人类糖尿病。胰岛素维持葡萄糖 通过两个主要机制的体内平衡：a）抑制肝葡萄糖 生产; b）刺激周围（肌肉）葡萄糖摄取。一次 葡萄糖被转运到细胞中，将其磷酸化至葡萄糖6- 磷酸盐（G-6-P）进入两种主要途径之一，糖原合成 和糖酵解。 反过来，糖酵解导致乳酸形成或 克雷布斯周期中的丙酮酸氧化，技术已经是 开发用于在体内测量胰岛素介导的葡萄糖的速率 人类的代谢。因此，在本研究中，我们建议检查 口服钒酸盐对葡萄糖耐受性的影响， 胰岛素介导的葡萄糖处置，葡萄糖氧化，糖酵解和 健康志愿者，IDDM和NIDDM受试者中的糖原合成。 这 将是一项安慰剂对照试验，以获取初步信息 关于此痕量元素的短期功效和安全性 人类主题。