Unger R H, Ketterer H, Dupré J, Eisentraut A M
J Clin Invest. 1967 Apr;46(4):630-45. doi: 10.1172/JCI105565.
The effects upon islet hormone secretion of highly purified preparations of secretin and of pancreozymin-cholecystokinin and of a crude gastrin-containing extract of hog antrum have been studied in acutely operated dogs. All three preparations were shown to cause a striking increase in insulin concentration in the pancreaticoduodenal venous plasma after their rapid endoportal injection in anesthetized dogs. With each hormone preparation, the peak in insulin secretion occurred 1 minute after injection, and a rapid decline was observed immediately thereafter. Whereas secretin and gastrin failed to alter significantly the pancreaticoduodenal venous glucagon or arterial glucose concentration, pancreozymin caused a dramatic rise in pancreaticoduodenal venous glucagon concentration, which reached a peak 3 minutes after injection, and hyperglycemia was noted to occur soon thereafter. Endoportal infusion of secretin and pancreozymin for 20 minutes caused responses that were sustained but qualitatively identical to the responses noted after rapid injection of the hormones. The beta-cytotropic effect of secretin was abolished by the infusion of epinephrine. These results could not be attributed to the small degree of contamination of the enteric hormone preparations with insulin or glucagon, and it would appear that secretin, pancreozymin, and probably gastrin have insulin-releasing activity and that pancreozymin has, in addition, glucagon-releasing activity.The demonstration that these three hormones possess insulin-releasing activity suggests that there is in the gastrointestinal tract a chain of betacytotropic hormones from antrum to ileum that is capable of augmenting insulin secretion as required for disposal of substrate loads. It is suggested that the existence of this "entero-insular axis" prevents high substrate concentrations that would otherwise follow ingestion of large meals were the insular response entirely a function of arterial substrate concentration.
在急性手术的犬身上，研究了高纯度的促胰液素制剂、促胰酶素-缩胆囊素制剂以及含粗制胃泌素的猪胃窦提取物对胰岛激素分泌的影响。在麻醉犬中，将这三种制剂经门静脉快速注射后，均显示可使胰十二指肠静脉血浆中的胰岛素浓度显著升高。每种激素制剂注射后1分钟胰岛素分泌达到峰值，随后立即快速下降。促胰液素和胃泌素未能显著改变胰十二指肠静脉中的胰高血糖素浓度或动脉血糖浓度，而促胰酶素可使胰十二指肠静脉中的胰高血糖素浓度急剧升高，注射后3分钟达到峰值，随后不久出现高血糖。经门静脉输注促胰液素和促胰酶素20分钟，引起的反应持续存在，但在性质上与快速注射激素后观察到的反应相同。输注肾上腺素可消除促胰液素的促β细胞作用。这些结果不能归因于肠激素制剂被胰岛素或胰高血糖素的轻度污染，似乎促胰液素、促胰酶素，可能还有胃泌素具有胰岛素释放活性，而且促胰酶素还具有胰高血糖素释放活性。这三种激素具有胰岛素释放活性的证明表明，胃肠道中存在一条从胃窦到回肠的促β细胞激素链，能够根据底物负荷的处理需要增加胰岛素分泌。有人提出，这种“肠-胰岛轴”的存在可防止在胰岛反应完全取决于动脉底物浓度时，因摄入大量食物而导致的高底物浓度。
