THE INTERNAL SECRETION OK THE PANCREAS 423 



That the pancreas possesses an internal secretory function 

 must be conceded upon general grounds. But the two-fold 

 significance attaching to the idea, and especially the earlier idea, 

 of internal secretion, namely, that of positive production together 

 with negative neutralization, suggests the possibility that the 

 regular pancreatic function may consist in the destruction of so- 

 called diabetogenic substances; that, after the extirpation of the 

 organ, these substances accumulate in the body; and that they 

 have a deleterious influence upon the normal metabolism of the 

 carbohydrates. This is a theory which has been advanced by 

 several authors (Hedon, in his first publication, Tuckett), and 

 w r hich seemed to derive support from Gaglio's statement, that 

 ligature of the thoracic duct prevents glycosuria after pancreasec- 

 tomy. This latter finding received no confirmation, however, 

 from later investigators (Lepine, Hedon, Biedl). The views of 

 Harley and of Vani are based upon de Domenicis's theory ; 

 both authors believe that the suppression of the pancreatic func- 

 tion gives rise to an auto-intoxication, the essential features of 

 which are severe nutritional disturbances, glycosuria, and nervous 

 symptoms being among the manifestations of the latter. Accord- 

 ing to Vani, this auto-intoxication is due to suppression of the 

 endocrinal function of the pancreas. 



The assumption that pancreatic diabetes is the outcome of an 

 auto-intoxication never obtained much support. It has since been 

 entirely abandoned ; for the hypothesis that auto-intoxication 

 occurs as the result of organic suppression becomes more and 

 more limited in its application, owing to the fact that proof of 

 the existence of toxic substances has never, as yet, been obtained. 

 The possibility was recently suggested by Zuelzer that, after 

 extirpation of the pancreas, harmful substances are retained in the 

 economy which, under normal circumstances, would be excreted 

 or destroyed by the agency of that organ. Zuelzer 's findings 

 permit, however, of a different interpretation. 



All the known facts concerning pancreatic diabetes, and 

 especially the profound changes in the metabolism of the carbo- 

 hydrates to which it gives rise, point unequivocally to suppression 

 of an internal pancreatic secretion which, under normal con- 

 ditions, plays a decisive role in the metabolism of the carbo- 

 hydrates as the originating cause of the condition. 



As evidence against a positive secretory function and forma- 

 tion of hormones by the pancreas, it is pointed out that the 

 brilliant results expected of organo-therapy have been conspicu- 

 ously absent in pancreatic diabetes. From all accounts, the 

 results of the administration of fresh or dried pancreas and the 

 subcutaneous injection of pancreatic extract, seem to be uncertain 

 both in clinical pancreatic diabetes and in the parallel condition in 

 animals deprived of their pancreas. The reports are, however, 

 exceedingly contradictory. Positive results were observed by 



