302 HORMONES 



tion theory is supported by the observation that removal of the liver 

 from either diabetic or normal animals is followed by an equally rapid 

 decline of blood glucose levels in both. Under these conditions at least, 

 the diabetic animal utilizes carbohydrate as. well as the normal one. 



All the symptoms of the disease are relieved by injection of insulin. 

 The hormone is not effective by mouth because it is destroyed by digestive 

 enzymes, as mentioned above. Excessive doses are sometimes adminis- 

 tered accidentally to diabetic patients. In such cases, as might be 

 expected, the blood sugar level falls sharply and may go so low as to 

 result in coma and, if not treated, death. This condition, insulin shock, 

 is counteracted quickly and completely by injection of glucose. Symp- 

 toms of insulin deficiency can be produced in animals by feeding alloxan, 

 and it has been suggested, but not proved, that alloxan may be in some 

 way connected with the development of diabetes. When present in the 

 body, its effect is to destroy the islet cells of the pancreas. 



HN C=0 



I I 



o=c c=o 



I I 



HN C=0 



Alloxan 



A condition closely resembling diabetes mellitus can be produced in 

 experimental animals by feeding the drug, ])hlorhizin, a glucoside present 

 in the root and bark of apple, pear, and plum trees. It has the follow- 

 ing chemical structure: 



CO-CH2— CH2-< /"OH 



OH 



Phlorhizin 



The blood sugar level in phlorhizin diabetes, however, is lower than 

 normal. The drug produces the symptoms of diabetes by preventing 

 the resorption of glucose by the tubules of the kidney, thus, in effect, 

 lowering the renal threshold and causing urinary excretion of sugar even 

 while the blood sugar level is in or below the normal range. 



The mechanism by which insulin acts is not definitely known. It 

 has been claimed by Cori and co-workers that insulin counteracts the 

 inhibition of hexokinase by hormones of the pituitary and adrenal glands. 

 However, the experimental results have been interpreted differently by 

 other workers, and the status of this suggestion, therefore, is still in 

 doubt. 



