1904] The Chemical Regulation of the Secretory Process. 317 



resting pancreas. One may say, therefore, that under healthy con- 

 ditions the activity of the pancreas is two-fold in character, and that 

 the normal stimulus of secretin excites not only a breaking down of 

 the protoplasm and a discharge of granules, but also a building up of 

 the protoplasm and a new formation of granules. So marked, in fact, 

 is this power of self-restitution that it is often advisable to diminish 

 the resistance of the animal by bleeding or other means if it is desired 

 to obtain a specimen of exhausted gland. 



A study by Mr. Dale of the stages of exhaustion carried out in this 

 way has brought to light a remarkable behaviour in the cells of the 

 pancreas, to which we have no analogies in other secreting glands of 

 the body. After the discharge of the granules the cells seem to 

 undergo a still further involution, losing the whole of their chromo- 

 phile substance, diminishing in size or undergoing vacuolation, and 

 finally being transformed into cells undistinguishable from those which 

 have long been known as forming the so-called " islets of Langerhans." 

 Mr. Dale has, in fact, shown that in all probability these " islets," 

 which are generally regarded as pre-formed structures, really repre- 

 sent stages in the functional activity of the secreting cells of the 

 gland, and he is of opinion that the activity of the gland is always 

 associated with a cycle of changes in which the islets are formed, to be 

 afterwards regenerated into secreting tissue. Other observers have 

 noted in the embryo a development of secreting tubules from tissue 

 undistinguishable from the " islets of Langerhans," and it is interesting 

 to note that the depletion of the gland caused by long starvation has 

 & similar effect to that caused by over-excitation, namely, the 

 conversion of a large proportion of the gland tissue into " islet " 

 tissue. 



Although secretin acts in this apparently coarse manner in turning 

 out all the pre-formed secretory products present at the time in the 

 pancreatic cells, the conditions of its formation determine a close 

 adaptation of the pancreatic activity to the needs of the animal. 

 Formation of secretin depends on the presence of acid chyme in the 

 duodenum. This acid chyme is squirted in small quantities into the 

 stomach at varying intervals after the taking of food. As soon as it 

 enters the gut, secretin is formed in the mucous membrane, absorbed by 

 the blood-vessels and carried to the pancreas, and it will continue to 

 be formed until the secreted pancreatic juice exactly neutralises the 

 acid of the intestinal contents. The presence of an excessive amount 

 of acid in the duodenum is prevented by the reflex pyloric mechanism 

 revealed by the researches of Von Mering and of Serdjunow.* These 

 observers have shown that so long as the contents of the duodenum 

 are acid the pylorus remains firmly closed. As soon, however, as they 

 become neutral or alkaline the pylorus opens and allows a further 

 * Pawlow, 'Da9 Experiment,' 1900, p. 17. 



