Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, 48109-5622, USA.
Am J Physiol Gastrointest Liver Physiol. 2011 Nov;301(5):G791-8. doi: 10.1152/ajpgi.00245.2011. Epub 2011 Aug 18.
Adaptive exocrine pancreatic growth is mediated primarily by dietary protein and the gastrointestinal hormone cholecystokinin (CCK). Feeding trypsin inhibitors such as camostat (FOY-305) is known to induce CCK release and stimulate pancreatic growth. However, camostat has also been reported to stimulate secretin release and, because secretin often potentiates the action of CCK, it could participate in the growth response. Our aim was to test the role of secretin in pancreatic development and adaptive growth through the use of C57BL/6 mice with genetic deletion of secretin or secretin receptor. The lack of secretin in the intestine or the secretin receptor in the pancreas was confirmed by RT-PCR. Other related components, such as vasoactive intestinal polypeptide (VIP) receptors (VPAC(1) and VPAC(2)), were not affected. Secretin increased cAMP levels in acini from wild-type (WT) mice but had no effect on acini from secretin receptor-deleted mice, whereas VIP and forskolin still induced a normal response. Secretin in vivo failed to induce fluid secretion in receptor-deficient mice. The pancreas of secretin or secretin receptor-deficient mice was of normal size and histology, indicating that secretin is not necessary for normal pancreatic differentiation or maintenance. When WT mice were fed 0.1% camostat in powdered chow, the pancreas doubled in size in 1 wk, accompanied by parallel increases in protein and DNA. Camostat-fed littermate secretin and secretin receptor-deficient mice had similar pancreatic mass to WT mice. These results indicate that secretin is not required for normal pancreatic development or adaptive growth mediated by CCK.
适应性外分泌胰腺生长主要由膳食蛋白质和胃肠激素胆囊收缩素 (CCK) 介导。已知喂食胰蛋白酶抑制剂（如法莫替丁 (FOY-305)）可诱导 CCK 释放并刺激胰腺生长。然而，法莫替丁也被报道可刺激分泌素释放，由于分泌素通常增强 CCK 的作用，它可能参与生长反应。我们的目的是通过使用缺乏肠分泌素或胰腺分泌素受体的 C57BL/6 小鼠来测试分泌素在胰腺发育和适应性生长中的作用。通过 RT-PCR 证实了肠道中缺乏分泌素或胰腺中缺乏分泌素受体。其他相关成分，如血管活性肠肽 (VIP) 受体 (VPAC(1) 和 VPAC(2)) 不受影响。分泌素增加了来自野生型 (WT) 小鼠的胰岛中 cAMP 的水平，但对缺乏分泌素受体的胰岛没有影响，而 VIP 和福斯可林仍诱导正常反应。体内分泌素未能诱导受体缺陷小鼠的液体分泌。缺乏分泌素或分泌素受体的小鼠的胰腺大小和组织学正常，表明分泌素对于正常的胰腺分化或维持不是必需的。当 WT 小鼠喂食含 0.1%法莫替丁的粉末饲料时，胰腺在 1 周内增大一倍，同时蛋白质和 DNA 也相应增加。用 camostat 喂养的 WT 小鼠的同窝分泌素和分泌素受体缺陷小鼠的胰腺质量与 WT 小鼠相似。这些结果表明，分泌素对于 CCK 介导的正常胰腺发育或适应性生长不是必需的。
