THE METABOLISM OF THE CARBOHYDRATES 681 



to the blood in the case of a completely diabetic animal, no change oc- 

 curs in the quotient. 



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 us 

 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 (liver) 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 depression of glycolytic power by these methods 

 prompted Knowlton and Starling 24 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 dia- 

 betic 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 100 gm. of heart substance per minute ; whereas that of a dia- 

 betic (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 permissible to assume that a much more striking difference 

 could be demonstrated when the perfusion fluid is made to traverse all 

 or practically all of the skeletal muscles, as well as the heart. For this 

 purpose an eviscerated animal may be employed that is, one in which 

 the abdominal viscera are removed after ligaticn of the celiac axis and 

 mesenteric arteries, and the liver is eliminated by mass ligation of its 

 lobes. Using such preparations, R. Gr. Pearce and Macleod 29 found that 

 the rate at which glucose disappears from the blood, although very 

 irregular, is in no way different in completely diabetic as compared 

 with normal dogs. They were thus unable to confirm any of Knowlton 

 and Starling's earlier conclusions. Patterson and Starling subsequently 

 pointed out that a serious error was involved in the earlier perfusion 

 experiments, partly on account of a remarkable but irregular disap- 

 pearance of glucose from the lungs, and partly because the diabetic 

 heart may contain a considerable excess of glycogen, from which its 



