Nature of the Pancreatic Autacoid 129 



There are various ways in which the prevention of an undue accumula- 

 tion and mobilisation of glucose and the consequent appearance of hyper- 

 glycemia might be supposed to be effected by an internal secretion of the 

 pancreas islets. 



(1) The active agent may itself be a glycolytic ferment (Lepine) and 

 may be the source of the glycolytic ferment which is known to be present 

 in blood. If so, removal or disease of pancreas would tend to produce 

 glycosuria in consequence of the absence of sufficient of this ferment to 

 effect the splitting of glucose, so that the sugar of the body would not be 

 metabolised further and would be passed out as such by the urine. As 

 against this theory, it is found that in diabetes the glycolytic power of the 

 blood is hot diminished ; and although in support of it the fact has been 

 urged that a glycolytic ferment can be got from the pancreas, it must be 

 pointed out that this is by no means peculiar to that organ, for a similar 

 enzyme is yielded by most organs and tissues of the body. 



(2) It may be of the nature of a kinase, the function of which is to 

 convert a pro-ferment into ferment, or perhaps to promote the activity of 

 an already existing ferment which serves to break down the molecule of 

 glucose and prepare it for ultimate oxidation in the muscles, liver, etc. In 

 support of this hypothesis it is stated by O. Cohnheim that a combination 

 of muscle juice with pancreas juice (obtained from the cells by hydraulic 

 pressure) is far more active glycolytically than either of the two employed 

 singly ; although, as Levene points out, the disappearance of sugar which 

 is caused cannot be definitely regarded as glycolysis. According to De 

 Meyer, a glycolytic pro-ferment which is activated by pancreas extract is 

 contained in the blood-leucocytes. Anything which tends to prevent the 

 formation of insuline, such as disease of the islet tissue, the entire removal 

 of the pancreas, and perhaps the action of adrenalin, would therefore 

 necessarily interfere with the glycolysis and prevent the utilisation of 

 glucose by the tissues, so that hyperglycemia and glycosuria would be 

 produced. According to this theory, the tissues of a depancreatised dog 

 should be unable or less able to utilise glucose for the production of muscular 

 work. Experiments on heart muscle which seemed to support this were 

 published by Knowlton and Starling. But other experiments by Porges 

 and Salomon (on skeletal muscle) gave a contrary result, and Starling has 

 since come to the conclusion that his results with Knowlton were within 

 the limits of individual variations of the normal heart muscle. 



(3) The substance {insvline) produced by the pancreas islets may be a 

 chalonic autacoid which tends to inhibit the formation of glucose from 

 glycogen, and incidentally to promote the storage of glycogen, so that in 

 its absence the glycogen which is present in the liver is rapidly converted 

 into glucose and the sugar absorbed from the alimentary canal or formed 

 in the body is not stored by the liver. The result again will be hyper- 

 glycemia and glycosuria. The fact that the conversion of glycogen into 

 glucose occurs rapidly in the excised liver seems to indicate that there is 



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