POSTPRANDIAL GLUCONEOGENESIS CONTRIBUTION TO GLUCOSE PRODUCTION IN DIABETICS

糖尿病患者餐后糖异生对葡萄糖生成的贡献

• 批准号: 6278031
• 负责人: ASHOK BALASUBRAMANYAM
• 金额: $ 2.57万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6278031
• 关键词: Mexican Americans; clinical research; fasting; gluconeogenesis; human subject; hypoglycemic agents; lipolysis; noninsulin dependent diabetes mellitus; nutrient intake activity; nutrition related tag; proteolysis; stable isotope double label

It is generally accepted that an increase in hepatic gluconeogenesis plays a significant role in the genesis of fasting hyperglycemia in NIDDM, but the effect of feeding on gluconeogenesis has not been carefully quantified in either health or in NIDDM. We have recently shown, using stable isotopes as tracers and mass isoptopomer analysis, that gluconeogenesis is not significantly suppressed by feeding even in normoglycemic, healthy Mexican-American men. Acarbose is a pseudo- oligosaccharide which competitively inhibits hydrolysis of carbohydrate by pancreatic amylase. We propose that an important mechanism of the beneficial glycemic effect of Acarbose is to decrease the component of post-prandial gluconeogenesis that arises from meal-derived three-carbon precursors formed in the gut. Ten NIDDM and 10 healthy Mexican-Americans will be enrolled in five experiments: 1) fasting-no Acarbose, U13C glucose; 2) fed-with acarbose, IV U13C glucose; 3) fed-without acarbose, IV U13C glucose; 4) fed-with acarbose, oral U13C glucose; and 5) fed-without acarbose, oral U13C glucose. During each of these experiments, IV 2H5 glycerol and 15N2 urea will be infused concurrently with the U13C glucose. Using stable isotopes as tracers and mass isoptopomer anlysis, we will obtain data which will enable us to determine the following: 1. the glucose flux and the contribution of gluconeogenesis to glucose flux during feeding in healthy and NIDDM Mexican-Americans; 2. the contribution of first-pass metabolism of dietary glucose to gluconeogenesis in the fed state; 3. the impact of consumption of Acarbose on first-pass metabolism of dietary glucose to three-carbon gluconeogenic precursors in the fed state; and 4. the contribution of lipolysis and proteolysis to gluconeogenesis in the fasting and fed states.

一般认为，肝再生的增加 在空腹高血糖症的发生中起着重要作用， NIDDM，但喂养对胚胎发育的影响尚未被证实。 在健康或NIDDM中仔细量化。 我们最近 显示，使用稳定同位素作为示踪剂和质量同位素分析， 即使在哺乳动物中， 血糖正常的健康墨西哥裔美国男性 阿卡波糖是一种伪- 竞争性抑制碳水化合物水解的寡糖 胰淀粉酶的作用 我们建议，一个重要的机制， 阿卡波糖的有益血糖作用是减少 膳食来源的三碳 前体在肠道中形成。 10名NIDDM患者和10名健康的墨西哥裔美国人将参加五个 实验：1）禁食-无阿卡波糖、U13 C葡萄糖; 2）喂食- 阿卡波糖，IV U13 C葡萄糖; 3）进食不含阿卡波糖，IV U13 C葡萄糖; 4） 喂食阿卡波糖，口服U13 C葡萄糖;和5）喂食阿卡波糖，口服 U13 C葡萄糖。 在这些实验的每一个中，IV 2 H5甘油和 15 N2尿素将与U13 C葡萄糖同时输注。使用 以稳定同位素为示踪剂，通过质量同位素分析， 这些数据将使我们能够确定以下内容：1。 葡萄糖 葡萄糖通量和葡萄糖代谢对葡萄糖通量的贡献 健康和NIDDM墨西哥裔美国人的喂养; 2. 的贡献 饮食中葡萄糖的首过代谢对胚胎发育的影响 进食状态; 3. 阿卡波糖用量对首过的影响 膳食葡萄糖代谢为三碳代谢前体 在进食状态下;以及4. 脂肪分解和蛋白质水解作用 在禁食和进食状态下的胚胎发育。