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This dissertation, Adrenomedullin in the Rat Digestive System: Response to Starvation by Siu-yin, Man, 文小燕, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Adrenomedullin in the Rat Digestive System: Response to Starvation Submitted by SIU YIN MAN for the Degree of Master of Philosophy at The University of Hong Kong in August 2005 Starvation has been shown to affect various physiological functions and peptide levels of the gastrointestinal tract. However, the effects of starvation on adrenomedullin (AM) levels in the digestive system have not been studied. Since AM has been shown to be present throughout the digestive system and may be an important regulator of gastrointestinal functions, we hypothesize that starvation may affect the AM system in the digestive system. The present study investigates the effects of acute (1-day) and chronic (4-day) starvation on the levels of immunoreactive-AM (ir-AM), and gene expressions of preproAM and AM receptors in the gastrointestinal system. The effects of acute starvation and AM on glucose uptake in isolated hepatocytes are also investigated. During acute starvation, only the gene expression of preproAM in the fundus of the stomach was up-regulated. After chronic starvation, the concentrations of ir-AM in both the fundus and pylorus were significantly increased. An up-regulation in preproAM gene expression was also detected in the pylorus. These changes might suggest that the secretion of AM might be reduced in the fundus but increased in the pylorus as starvation was prolonged. Moreover, marked reductions in the gene expressions of fundic calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP) 3 as well as the pyloric CRLR and RAMP2 were observed in the chronically starved rats. Regarding the pancreas, the ir-AM contents were reduced following chronic starvation, suggesting a possible increase in the inhibitory action of AM on pancreatic insulin release. In the liver, the CRLR mRNA expression was found to be down-regulated. The lack of changes in plasma ir-AM levels in the courses of acute and chronic starvation was strongly suggestive of the paracrine action of AM in the digestive system. In the liver, AM immunoreactivity was detected in the parenchymal and stellate cells lining the sinusoid, suggesting that AM might play a role in the regulation of hepatic metabolism and circulation. In isolated hepatocytes from acutely starved rats, the uptake of glucose, glycerol and alanine was markedly lower than those from the fed rats. A high AM concentration (1000 nM) increased the insulin-stimulated glucose uptake by more than 2-fold whereas lower AM concentrations (10 and 100 nM) reduced the glucagon-induced alanine uptake. The gene expression of RAMP1 was up-regulated by glucose and that of preproAM was increased by glycerol. In similar preparations from fed rats, 1000 nM AM enhanced the basal and insulin-induced glucose uptake. Both glucose and glycerol were found to increase the gene expressions of preproAM and RAMP1. These findings showed that AM might play some roles in the modulation of glucose uptake in hepatocytes. The present study suggests that acute starvation may increase the secretion of AM in the fundus. During chronic starvation, the release of AM may be reduced in the liver and fundus but may be augmented in the pancreas and pylorus. In isolated hepatocytes from acutely starved rats, the uptake of glucose is reduced whereas a high concentration of AM can increase the insulin-induc

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