Hunterian Laboratory of Experimental Pathology of the Johns Hopkins University, Baltimore.
J Exp Med. 1916 Dec 1;24(6):621-50. doi: 10.1084/jem.24.6.621.
The experiments indicate that the pancreas, when perfused aseptically with Locke's solution containing physiological concentrations of dextrose, does not alter the reducing properties of the perfused solution. The pancreas, however, seems to supply something to the Locke's solution circulating through its arteries which in some way brings about a utilization of sugar by the living heart to an extent that does not occur with the heart alone. This pancreatic substance possesses some of the characteristics of an enzyme. It is inactivated by boiling; it is unstable, rapidly becoming inactive on standing; it acts in small amounts; it causes a great acceleration in the rate of a reaction which otherwise proceeds slowly, and the rate of reaction diminishes as the reaction proceeds. Thus this substance has more of the characteristics of an enzyme than of a stable internal secretion like that of the adrenal glands. The disappearance of sugar was dependent upon the presence of living heart tissue, and it ceased as soon as the perfusate was removed from the heart-pancreas circulation and did not occur at all when a pancreatic perfusate was passed through a non-beating heart. This result indicates that the reaction is not similar to that obtained when muscle and pancreas extracts act on more concentrated solutions of dextrose. The living heart in the presence of the pancreatic factor and dextrose, is responsible for two effects. First, a condensation of the sugar to a non-reducing form that yields again a simple sugar on hydrolysis or by simply standing, with a preservative, at 37 degrees C. for 24 hours. Second, a disappearance of sugar which is probably due to its destruction by hydrolysis or oxidation. After deducting the reducing sugar in the heart-pancreas perfusions which could be recovered by hydrolysis, the amount of sugar which had actually disappeared exceeded that which was used by the heart when perfused with dextrose alone. As to the fate of this portion of the sugar, no definite evidence was obtained. The question arises as to whether this substance obtained from the perfused pancreas is identical with the hypothetical internal secretion of the pancreas so essential in sugar metabolism. That there is an internal secretion of the pancreas which can be obtained by this method, and that in some way it accelerates the utilization of sugar by the living heart, seems evident. Though the conclusions are based on the heart and pancreas isolated from the numerous interrelating factors occurring in the body, the evidence suggests, at least, that the substance or substances obtained by perfusing the pancreas may be concerned in the normal activity of the pancreas upon sugar metabolism.
实验表明,当用含有生理浓度葡萄糖的 Locke 溶液无菌灌注胰腺时,胰腺不会改变灌注溶液的还原性质。然而,胰腺似乎向其动脉循环中的 Locke 溶液提供了某种物质,这种物质以某种方式促进了活心脏对糖的利用,而单独使用心脏则不会发生这种情况。这种胰腺物质具有某些酶的特性。它会被煮沸失活;它不稳定,静置时很快失活;它的作用量很小;它会极大地加速反应速度,而这种反应本身进行得很慢,随着反应的进行,反应速度会降低。因此,这种物质比像肾上腺那样稳定的内分泌物质更具有酶的特性。糖的消失依赖于活心脏组织的存在,一旦将灌流液从心脏-胰腺循环中取出,糖的消失就会停止,而当将胰腺灌流液通过不跳动的心脏时,根本不会发生这种情况。这个结果表明,这种反应与肌肉和胰腺提取物作用于更浓的葡萄糖溶液时获得的反应不同。在胰腺因子和葡萄糖存在的情况下,活心脏负责两个作用。首先,将糖浓缩成非还原形式,然后在 37°C 下通过水解或简单静置,在防腐剂存在下 24 小时再次产生简单糖。其次,糖的消失,可能是由于其水解或氧化而被破坏。扣除通过水解可从心脏-胰腺灌注中回收的还原糖后,实际上消失的糖量超过了单独用葡萄糖灌注心脏时的消耗量。至于这部分糖的命运,没有得到明确的证据。由此产生一个问题,即从灌注的胰腺中获得的这种物质是否与糖代谢中必不可少的胰腺假设内泌物相同。显然,胰腺有一种可以通过这种方法获得的内泌物,它以某种方式加速了活心脏对糖的利用。尽管这些结论是基于从身体中存在的众多相互关联的因素中分离出来的心脏和胰腺得出的,但这些证据至少表明,通过灌注胰腺获得的物质或物质可能与胰腺对糖代谢的正常活动有关。