712 METABOLISM 



The Pathogenesis of Pancreatic Diabetes 



The certainty with which diabetes results from pancreatectomy in dogs, 

 as well as the frequent occurrence of demonstrable lesions of the pan- 

 creas in diabetes in man, leaves no doubt that this gland must be in some 

 way essential in the physiological breakdown of carbohydrates in the 

 normal animal, but how, we can not at present tell. All we know is 

 that the first change to occur after the gland is removed is a sweeping 

 out of all 'but a trace of the glycogen of the liver, although the glycogen of 

 the muscles may remain ; indeed, in the cardiac muscle there may be more 

 than the usual amount. 28 Nor can any glycogen be stored in the liver when 

 excess of carbohydrates is fed. After the glycogen has disappeared, 

 gluconeogenesis sets in, so that the tissues come to melt away into sugar, 

 and all the symptoms of acute starvation, associated with certain others 

 that are possibly due to a toxic action of the excess of sugar and of other 

 abnormal products in the blood such as ketone bodies make their appear- 

 ance. 



Accompanying the gluconeogenesis another very definite abnormality in 

 metabolism becomes evident namely, an inability of the tissues to ~burn 

 sugar. This fact is ascertained by observing the respiratory quotient. 

 When glucose is added to the blood in the case of a completely diabetic 

 animal, no change occurs in the quotient, whereas in normal animals 

 under such conditions it rises almost to 1.0 (cf. page 582). 



There are, therefore, two essential disturbances of carbohydrate 

 metabolism in pancreatic diabetes overproduction of sugar and aboli- 

 tion of the ability of the tissues to use it. It becomes important for UP 

 to see whether the tissues exhibit this inability to use sugar when they 

 are isolated from the animal ; for if they should, a much more searching 

 investigation of the essential cause of their inability would be possible 

 than is the case when they are functioning along with the other organs 

 and tissues. 



The earlier experiments, of Lepine and his pupils, which seemed to show that diabetic 

 blood did not possess the glycolytic power of normal blood; and those of Cohnheim, 

 from which it was concluded that mixtures of the expressed juices of muscle and 

 pancreas, although ordinarily destroying glucose, failed to do so when they were taken 

 from a diabetic animal, are now known to be erroneous. The failure to show a depres- 

 sion of glycolytic power by these methods prompted Knowlton and Starling 2 * to 

 investigate the question whether any difference is evident in the rate with which glucose 

 disappears from a mixture of blood and saline solution used to perfuse a heart outside 

 the body, according to whether the heart was from a normal or a diabetic dog. In 

 the first series of observations which these workers made, it was thought that the 

 normal heart used glucose at the rate of about 4 mg. per gram of heart substance 

 per hour; whereas that of a diabetic (depancreatized) animal used less than 1 mg. 

 If such striking differences in the rate of sugar consumption could make themselves 

 manifest for so relatively small a mass of muscular tissue as that of the heart, it is 



