POSTPRANDIAL GLUCONEOGENESIS CONTRIBUTION TO GLUCOSE PRODUCTION IN DIABETICS

人们普遍认为，肝脏糖异生的增加 在空腹高血糖的发生中起重要作用 NIDDM，但摄食对糖异生的影响尚未得到 在健康或非胰岛素依赖型糖尿病中仔细量化。我们最近做了 显示，使用稳定的同位素作为示踪剂和质量同分异构体分析， 即使喂食也不会显著抑制糖异生 血糖正常、健康的墨西哥裔美国男性。阿卡波糖是一种假性的 竞争性地抑制碳水化合物的水解的低聚糖 通过胰淀粉酶。我们建议一个重要的机制 阿卡波糖的降血糖作用是降低其主要成分 餐后糖异生，源于膳食来源的三碳 在肠道中形成的前体。 10名NIDDM和10名健康的墨西哥裔美国人将在5年内登记 实验：1)禁食--不含阿卡波糖，U13C葡萄糖；2)喂食 阿卡波糖，静脉注射U13C葡萄糖；3)喂食-不含阿卡波糖，静脉注射U13C葡萄糖；4) 喂食阿卡波糖，口服U13C葡萄糖；和5)喂食-不含阿卡波糖，口服 U13C葡萄糖。在每个实验中，IV 2H5甘油和 15N尿素将与U13C葡萄糖同时输注。vbl.使用 作为示踪剂的稳定同位素和质量异构体分析，我们将获得 使我们能够确定以下内容的数据：1.葡萄糖 糖异生对葡萄糖通量的贡献 在健康和非胰岛素依赖型糖尿病墨西哥裔美国人中喂养；2.贡献 饮食中葡萄糖的首次代谢对糖异生的影响 FED状态；3.阿卡波糖消费对首过的影响 膳食葡萄糖对三碳糖异生前体的代谢 在联邦状态下；4.脂肪分解和蛋白质分解的贡献 禁食和进食状态下的糖异生。

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.