POSTPRANDIAL GLUCONEOGENESIS TO GLUCOSE PRODUCTION IN NORMAL VS NIDDM

正常人与 NIDDM 中餐后糖异生对葡萄糖产生的影响

• 批准号: 6264741
• 负责人: ASHOK BALASUBRAMANYAM
• 金额: $ 3.6万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264741
• 关键词: Mexican Americans; clinical research; diabetes mellitus therapy; fasting; food; gluconeogenesis; glucose metabolism; human subject; human therapy evaluation; hyperglycemia; hypoglycemic agents; liver metabolism; male; noninsulin dependent diabetes mellitus; nutrient intake activity; nutrition related tag; stable isotope

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. Eight NIDDM and 8 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.

人们普遍认为，肝再生的增加在NIDDM空腹高血糖的发生中起着重要作用，但在健康或NIDDM中，进食对肝再生的影响尚未被仔细量化。 我们最近发现，使用稳定同位素作为示踪剂和质量同位素分析，即使在血糖正常的健康墨西哥裔美国男性中，进食也不会显著抑制新生儿的发育。 阿卡波糖是一种假寡糖，其竞争性抑制胰淀粉酶水解碳水化合物。我们提出阿卡波糖有益血糖效应的一个重要机制是减少餐后代谢的成分，该成分来自肠道中形成的膳食来源的三碳前体。8名NIDDM患者和8名健康墨西哥裔美国人将参加5项实验：1）禁食-无阿卡波糖，U13 C葡萄糖; 2）进食-阿卡波糖，IV U13 C葡萄糖; 3）进食-无阿卡波糖，IV U13 C葡萄糖; 4）进食-阿卡波糖，口服U13 C葡萄糖;和5）进食-无阿卡波糖，口服U13 C葡萄糖。 在这些实验中，IV 2 H5甘油和15 N2尿素将与U13 C葡萄糖同时输注。 利用稳定同位素作为示踪剂，通过同位素质量分析，我们将获得一些数据，这些数据将使我们能够确定以下几点：1。 健康和NIDDM墨西哥裔美国人在进食过程中的葡萄糖流量和葡萄糖生成对葡萄糖流量的贡献; 2. 在进食状态下，膳食葡萄糖的首过代谢对胚胎发生的贡献; 3. 进食状态下阿卡波糖摄入量对膳食葡萄糖首过代谢为三碳益生菌前体的影响;以及4. 在禁食和进食状态下脂肪分解和蛋白质水解对脂肪生成的贡献。