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.
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