セクレチンの膵内外分泌作用に関する研究:第4編合成セクレチンのラットin vivoにおける膵内外分泌作用

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In the previous studies we have shown that endogenous secretin induced by an intraduodenal instillation of 0.1N HCl or 1-phenyl-1-hydroxy-n-pentane is not able to stimulate insulin secretion, but exogenous synthetic secretin stimulates pancreatic a-cells in the rat pancreas perfused with glucose 50mg/dl. Contrary to these findings, many investigators have reported that natural porcine secretin can stimulate insulin secretion in man and in the dog.<BR>However, none of the previous reports have determined plasma secretin levels after an exogenous secretin administration. Thus it was not obvious whether insulin-releasing effect of secretin was physiological or pharmacological. Therefore, the present investigation was undertaken to make clear two questions. One was to evaluate the pancreatic endocrine and exocrine secretions in response to a bolus injection of synthetic secretin in the rat. The other was to compare the secretin levels in the portal vein introduced by the bolus injection with that endogenously released by HCl. We also discussed the endocrine and exocrine secretions in response to synthetic secretin after pretreatment of 1mg per kg B.W. atropine sulphate, since in the in vitro perfused rat pancreas, synthetic secretin did not show a direct effect on the pancreatic β-cell. Wistar strain male rats, weighing from 250g B.W. to 300g B.W. were used after a 15 hr starvation period and were anesthetized by a subcutaneous injection of pentobarbital. Various amounts of synthetic secretin (10ng/kg B.W. to 100μg/kg B.W.) were introduced into the jugular vein by a single injection. The flow rate of pancreatic juice and amylase output were measured at 10 min intervals. Plasma insulin, glucagon and secretin in the portal vein were determined by radioimmunoassay.<BR>Immunoreactive insulin (IRI) secretion rapidly occurred in response to 10μg/kg B.W. synthetic secretin. However, the concentration of immunoreactive secretin (IRS, 28.7 ± 4.1ng/ml) at this time was 80 times heigher than the physiological level (351.5 ± 28.4pg/ml) released by 0.1N HCl. Therefore IRI response stimulated by a bolus injection of synthetic secretin may be due to the pharmacological effect of secretin or to the effect of other factors. In contrast to IRI, immunoreactive glucagon (IRG) increased significantly at the same secretin dose of 10ng/kg B.W. as exocrine secretions did. These endocrine secretions in response to 10μg/kg B.W. secretin were suppressed significantly after the pretreatment of atropine sulphate, whereas exocrine secretions were not changed.<BR>The vagal nerve seems to play a significant role on the effect of synthetic secretin on insulin secretion in in vivo rat experiments since insulin secretion in response to synthetic secretin could not be detected in the perfused rat pancreas without a nervous system.
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セクレチンの膵内外分泌作用に関する研究:第4編合成セクレチンのラットin vivoにおける膵内外分泌作用

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セクレチンの膵内外分泌作用に関する研究:第4編 合成セクレチンのラットin vivoにおける膵内外分泌作用

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セクレチンの膵内外分泌作用に関する研究:第4編合成セクレチンのラットin vivoにおける膵内外分泌作用