STUDY OF DISEASE 



hypothesis either that the hexose phosphate which arises is not 

 hydrolyzed or that, owing to its structural abnormahty, the 

 glycogen is not sensitive to attack even by active phosphorylase. 

 In this regard it is of interest that patients deficient in pancreatic 

 islet a-cells, the apparent source of glucagon, have recently been 

 described (11). Hypoglycemia was noted to occur in these 

 subjects. 



Even assuming all the requisite enzyme systems in the liver 

 to be intact, clearly if there is no glycogen in the liver, glyco- 

 genolysis must cease to play a role as a source of blood glucose. 

 Virtually total depletion of hepatic glycogen ensues upon 

 relatively brief periods of inanition, and marked decreases in the 

 content of glycogen in the liver have been observed in a variety 

 of conditions, including exposure to low oxygen tension or 

 intoxication with thyroxin or thyroglobulin. It follows that 

 under these circumstances, hepatic glycogenolysis cannot be 

 relied upon as a source of blood sugar. 



An apparently distinct mechanism which can be altered in 

 disease but which also affects the rate at which the liver con- 

 tributes glucose to the blood is gluconeogenesis. Profound 

 changes may be elicited in the experimental animal, and analo- 

 gous situations may be observed in clinical material wherein 

 variations in adrenocortical activity result in changes in the rate 

 at which amino acids are deaminated and glucose is formed. 

 In general terms, the presence of excessive amounts of the 11- 

 oxysteroids of the adrenal cortex results in the generation of 

 large amounts of glucose from noncarbohydrate precursors (22), 

 a rise in the total carbohydrate content of the organism, and 

 incidentally a rise in blood glucose concentration. Conversely, 

 in the adrenalectomized animal or Addisonian patient, with 

 glucogenesis from noncarbohydrate sources impeded, hypo- 

 glycemia may be encountered. In contrast to the state of 

 present knowledge of the mode of action of epinephrine or of 

 glucagon, no generally acceptable hypothesis can be offered to 

 account for this action of the corticosteroids. 



Defects in the utilization of blood glucose are if anything 



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