SECRETION. 235 



of the individual cells are not clearly distinguishable, but it can be seen that 

 there are two zones, one clear and homogeneous on the side toward the basement 

 membrane, and one granular on the side toward the lumen. During activity 

 the secretory tubules show a notched appearance corresponding to the positions 

 of the cells, the outlines of the cells become more distinct, the granular zone 

 becomes smaller, and the homogeneous zone increases in width. It should be 

 stated also that in this latter condition the basal zone of the cells shows a dis- 

 tinct striation. From these appearances we must believe that, as in the case 

 of the salivary gland, a part at least of the organic material of the secretion is 

 formed from the granules of the inner zone, and that the granules in turn are 

 formed within the cells from the homogenous material of the outer zone. 



Enzyme and Zymogen. — The observations just described indicate that the 

 enzymes of the pancreatic secretion are derived from the granules in the cells, 

 but other facts show that the granules do not contain the enzymes as such, but 

 a preparatory material or mother-substance to which the name zymogen 

 (enzyme-maker) is given. This belief rests upon facts of the following kind : 

 If a pancreas is removed from a dog that has fasted for twenty-four hours, 

 when, as we have seen, the cells are heavily loaded with granules, and a glycerin 

 extract is made, very little active enzyme will be found in it. If, however, 

 the gland is allowed to stand for twenty-four hours in a warm spot before the 

 extract is made, or if it is first treated with dilute acetic acid, the glycerin ex- 

 tract will show very active tryptic or amylolytic properties. Moreover, if an 

 inactive glycerin extract of the perfectly fresh gland is treated by various 

 methods, such as dilution with water or shaking with finely divided platinum- 

 black, it becomes converted to an active extract capable of digesting proteid 

 material. These results are readily explained upon the hypothesis that the 

 granules contain only zymogen material, which during the act of secretion, or 

 by means of the methods mentioned, may be converted into the corresponding 

 enzymes. As the three enzymes of the pancreatic secretion seem to be distinct 

 substances, one may suppose that each has it own zymogen to which a distinc- 

 tive name might be given. The zymogen that is converted into trypsin is 

 frequently spoken of as trypsinogen. 



Normal Mechanism of Pancreatic Secretion. — Alter the establishment 

 of a pancreatic fistula it is possible to study the flow of secretion in its rela- 

 tions to the ingestion of food. Experiments of this kind have Ween made. 

 They show that in animals like the dog, in which sufficient food may be taken 

 in a single meal to last for a day, the flow of secretion is intimately connected 

 with the reception of food into the stomach and its subsequent digestiv 

 changes. The time relations of the secretion to the ingestion of food are 

 shown in the accompanying chart (Fig. 61). The secretion begins immedi- 

 ately after the food enters the stomach, and increases in velocity up to a cer- 

 tain maximum which is reached some time between the first and the third hour 

 after the meal. The velocity then diminishes rapidly to the fifth or sixth 

 hour, after which there may be a second smaller increase reaching its maxi- 

 mum about the ninth to the eleventh hour. From this point the secretion 



