セクレチンの膵内外分泌作用に関する研究:第1編・十二指腸内塩酸ならびにI-Phenyl-I-Hydroxy-n-Pentane注入と合成セクレチン静脈内投与に対する血中セクレチン濃度と膵外分泌反応の比較

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A demonstration of the greater effect of oral glucose administration, as compared with intravenous administration, in stimulating a rise in serum insulin levels led to the hypothesis that during the passage through the gastrointestinal tract ingested glucose induces the release of intestinal factors which augment the beta-cytotropic effect of glucose. Recent work has suggested that secretin, a hormone which can be extracted from duodenal mucosa, has a significant insulinotropic effect in vivo and in vitro. Intestinal acidification is presently the only recognized stimulus for the secretion of secretin. However, widely different results have been obtained by several laboratories concerning the beta-cytotropic action of endogenous secretin. Furthermore, overestimation of secretin release calculated on the basis of pancreatic bicarbonate secretion after intraduodenal instillation of HCl may indicate that intestinal acidification causes a release of not only secretin but also other stimulators of pancreatic exocrine and endocrine secretion. In the present study we investigated the effect of intraduodenal infusion of HC1 or 1-phenyl-1-hydroxy-n-pentane (PHP) on the concentration of immunoreactive secretin in portal plasma and pancreatic exocrine secretion, and compared it with that of intravenous synthetic secretin to further evaluate the beta-cytotropic effect of endogenous secretin. In addition, the effect of somatostatin on HCl-stimulated secretin and pancreatic exocrine secretion was investigated. Male Wistar rats weighing 250-300g and fasted overnight were used in all experiments. Under pentobarbital anesthesia, the abdomen was opened through a midline incision. A polyethylene catheter was inserted into the bile duct at the proximal end to drain out the bile. For measurement of pancreatic exocrine secretion, a calibrated capillary tube was attached to the free end of the pancreatic cannula which was inserted into the distal end of the common bile duct at a point shortly before it entered the duodenum. Every 10 min, the capillary tube was replaced and the rate of flow of the pancreatic juice down the tube was measured for an hour. A sample of the juice was diluted with physiological saline of 500μl and stored at-20°C until amylase assay. Blood samples were obtained through a polyethylene catheter placed in the portal vein. Infusion of the duodenum was accomplished by a catheter inserted through an incision in the stomach into the duodenal bulb and kept in place by means of a tight ligature around the pylorus. Care was taken not to damage or ligate the gastroepiploic vessels. The following solutions were constantly introduced into the duodenum for 2 min (2ml/min) : 0.1N-HCl, 200mg/kg/2ml PHP, and 2.5% arabic gum solution (placebo). Synthetic secretin, dissolved in isotonic saline, was infused into the jugular vein for 20 min with a syringe pump at a rate of 10ng/kg/min. Somatostatin was dissolved in saline and administered intravenously by a syringe pump for 30 min, starting 10 min before the intraduodenal instillation of HC1 and continuing for a further period of 20 min (50μg/kg/h). Plasma secretin concentrations were determined by radioimmunoassay using the double antibody method. Amylase activity in the pancreatic juice was assayed by the chromogenic method using blue-dyed starch polymer. Both 0.1N-HC1 and the 200mg PHP infusion elicited a rapid immunoreactive secretin (IRS) increase, reaching a peak value (HCl : 374.6 ± 26.3, PHP : 335.4 ± 68.9pg/ml) at 5 min. An acid load of 0.4mEq resulted in pancreatic amylase release about 12 times higher than the value obtained with the PHP instillation and synthetic secretin infusion (HCl : 2130.2 ± 250.9, PHP : 173.5 ± 22.8, intravenous secretin : 281.9 ± 62.3 Somogyi Units/10 min), though the portal venous IRS levels and the flow rate of the pancreatic juice were nearly the same.
日本内分泌学会の論文

セクレチンの膵内外分泌作用に関する研究:第1編・十二指腸内塩酸ならびにI-Phenyl-I-Hydroxy-n-Pentane注入と合成セクレチン静脈内投与に対する血中セクレチン濃度と膵外分泌反応の比較

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