The long term objectives of this study are to determine the regulation of intestinal metabolism of glutamine and glucose and the effect of this metabolism on portal venous concentration to glucose, glutamine, lactate and alanine. The rate of synthesis of liver glycogen is controlled by portal venous concentrations of glucose, lactate and glutamine. In the small intestine glucose is oxidized to lactate under aerobic conditions, while glutamine is the primary oxidative substrate. The metabolism of glucose to lactate is an important component of the digestive process since the liver utilizes lactate for glycogen and fatty acid synthesis.
Specific Aims : 1. Utilizing a chronically catheterized portal venous rat model serum glucose, glutamine, lactate and alanine will be measured during both fasting and refeeding periods. 2. Using tissue slices, and isolated enterocytes (crypt and villus) and isolated mitochondria, changes in glucose and glutamine metabolism to lactate, CO2 and alanine during fed and fasting states will be determined. Intramitochondrial and cytosolic [NADH]/[NAD+], adenine nucleotide content, energy charge, electron transport chain activity, the shuttle of NADH into mitochondria, the interaction of LDH and pyruvate dehydrogenase will be determined on whole tissue and isolated cells. These regulatory mechanisms will be correlated to changes in portal venous concentrations of glucose, lactate, glutamine and alanine in rats on fasting, high protein and high carbohydrate diets. 3. Changes in the metabolic regulatory parameters will be repeated on villus cells of suckling and postweaned rats. 4. The effect of glucocorticoids and/or thyroxine on the metabolism of glutamine, glucose and the metabolic parameters described above in whole tissue and isolated villus and crypt cells of suckling rat will be determined. Glucocorticoids and thyroxine induce maturation of enterocytes and their metabolism during the suckling-weaning period. These studies will demonstrate regulatory effect of intracellular metabolism of absorbed substrates on portal venous substrate concentrations in the fed versus fasted rat and the suckling versus postweaned rat. In premature infants that are nutritionally supported by hyperalimentation, the processing of the intestine is by-passed. An understanding of the physiological effect of intestinal metabolism during development on portal venous substrate concentration is important in developing appropriate substrates during hyperalimentation since liver function is regulated by portal venous substrate concentration.
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| Kimura, R E; LaPine, T R; Johnston, J et al. (1988) The effect of fasting on rat portal venous and aortic blood glucose, lactate, alanine, and glutamine. Pediatr Res 23:241-4 |
