Müller M K, Goebell H, Alfen R, Ehlers J, Jäger M, Plümpe H
Department of Medicine, University of Essen, West Germany.
J Nutr. 1988 May;118(5):645-50. doi: 10.1093/jn/118.5.645.
The effects of chronic oral treatment of rats with 400 mg/kg body weight camostat, a synthetic protease inhibitor, on weight gain and both pancreatic exocrine and endocrine secretion were studied and compared with pair-fed controls. Administration of camostat was found to result in a lower weight gain than in untreated rats fed ad libitum because of reduced food intake. The pancreas of treated rats showed hypertrophy and hyperplasia with significantly higher total contents of amylase, lipase, trypsinogen and chymotrypsinogen than that of pair-fed controls. The specific activity of lipase, trypsinogen and chymotrypsinogen remained unchanged but the specific activity of amylase was significantly lower than in pair-fed controls. Stimulation of pancreatic enzymes with CCK 8 in treated rats resulted in a greater output of proteases, no difference in secretion of lipase and a lower secretion of amylase than in pair-fed rats. Glucose-dependent insulin secretion was also significantly lower in camostat-treated rats than in controls. This effect could be reversed by gastric inhibitory polypeptide. After termination of treatment with camostat all enzymes were normalized within 14 d. Our results on the hypertrophied pancreas of rats suggest preferential synthesis and secretion of protease at the expense of amylase and diminished sensitivity of insulin to stimulation by glucose. All effects of camostat on the pancreas were reversible.
研究了以400mg/kg体重的合成蛋白酶抑制剂抑肽酶对大鼠进行长期口服治疗，对体重增加以及胰腺外分泌和内分泌分泌的影响，并与配对喂养的对照组进行比较。发现给予抑肽酶后，由于食物摄入量减少，体重增加低于自由采食的未治疗大鼠。治疗大鼠的胰腺显示肥大和增生，淀粉酶、脂肪酶、胰蛋白酶原和糜蛋白酶原的总含量明显高于配对喂养的对照组。脂肪酶、胰蛋白酶原和糜蛋白酶原的比活性保持不变，但淀粉酶的比活性明显低于配对喂养的对照组。用CCK-8刺激治疗大鼠的胰腺酶，导致蛋白酶的分泌量增加，脂肪酶分泌无差异，淀粉酶分泌低于配对喂养的大鼠。抑肽酶治疗的大鼠中葡萄糖依赖性胰岛素分泌也明显低于对照组。这种作用可被胃抑制多肽逆转。停止用抑肽酶治疗后，所有酶在14天内恢复正常。我们对大鼠肥大胰腺的研究结果表明，以牺牲淀粉酶为代价优先合成和分泌蛋白酶，以及胰岛素对葡萄糖刺激的敏感性降低。抑肽酶对胰腺的所有作用都是可逆的。
