STUDY OF DISEASE 



in the intact mammal, and its presence must be regarded as an 

 unexplained biochemical curiosity. Whether hepatic glucose 

 dehydrogenase is a vestigial compound or whether it is a truly 

 important enzyme, the proper substrate of which has not been 

 identified, remains to be determined. 



In addition to the foregoing fates, glucose may be lost to the 

 mammalian organism in the intestinal and urinary tracts. In 

 the intestinal tract, failure of adequate polysaccharide digestion 

 or excessive bacterial fermentation deprives the mammal of a 

 portion of ingested carbohydrate. Whereas normal sugar losses 

 in the urine are negligible, these become significant if either the 

 normal renal threshold is exceeded by an abnormal hyper- 

 glycemia or normal blood is circulating through kidneys with 

 an abnormally low glucose threshold. 



In consideration of the numerous sources and fates of blood 

 glucose, it is certainly not surprising that there are many disease 

 states which result in alterations, positive or negative in sign, of 

 glucose concentration in the blood. Still other defects in one or 

 another mechanism might be anticipated to produce alterations 

 in blood glucose concentration but fail to do so as a consequence 

 of homeostatic mechanisms that are invoked. Thus simple 

 failure to ingest carbohydrate or failure to digest polysaccharide, 

 as may occur in pancreatic disease or diarrhea, will not, in 

 general, cause profound hypoglycemia. This is at least in part 

 explained by a compensatory decline in glucose utilization by 

 cells of the liver and is reflected in a diminished consumption of 

 glucose for hepatic lipogenesis in the intact animal (3) as well as 

 in the liver slice (24). Failure of the intestinal mucosa actively 

 to transport glucose from the lumen to the portal blood is seen 

 in sprue, and this situation also rarely leads to hypoglycemia. 

 The site of the defect is readily demonstrable clinically, however, 

 by the finding of a normal intravenous glucose tolerance in the 

 face of a failure of blood glucose to rise after oral administration. 

 It is noteworthy that the defect in sprue can be simulated by the 

 application of phlorhizin to the intestinal mucosa (10). 



The liver normally supplements the intestinal tract as a 



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