88 ESSENTIALS OF CHEMICAL PHYSIOLOGY 



close relationship of sugar and glycuronic acid is shown by the following 



formulae : 



COH COH 



(CHOH) 4 (CHOH) 4 



CH 2 OH COOH 



[dextrose] [glycuronic acid] 



That is, two hydrogen atoms in the CH 2 OH group are replaced by one of 

 oxygen. This oxidation is readily brought about in the body, and glycuronic 

 acid is usually found in diabetic urine ; but the further oxidation into water 

 and carbon dioxide is a more difficult task, because it involves the disruption 

 of the linkage of the carbon atoms. Perhaps it is here that the internal 

 secretion of the pancreas is effective. This, however, is at present a mere 

 theory, and certainly Lepine's idea that the ferment of the pancreatic 

 internal secretion is one which initiates glycolysis or sugar-splitting in the 

 blood, has been abundantly disproved. It may be that the active principle 

 of the pancreatic internal secretion stimulates the glycolytic action of the 

 tissue -cells. It is conceivable that in the other great cause of experimental 

 glycosuria. namely, injury to nervous structures, as in Bernard's puncture 

 experiment, the derangement of the nervous system exerts some unknown 

 influence on the pancreas as well as on the liver. 



Many poisons produce temporary glycosuria, but the most interesting 

 and powerful of these is phloridzin. The diabetes produced is very intense. 

 Phloridzin is a glucoside, but the sugar passed in the urine is too great to be 

 accounted for by the small amount of sugar derivable from the drug. 

 Besides that, phloretin, a derivative of phloridzin, free from sugar, produces 

 the same results. 



Phloridzin produces diabetes in starved animals, or in those in which any 

 carbohydrate store must have been got rid of by the previous administration 

 of the same drug. Phloridzin-diabetes is therefore analogous to those intense 

 forms of diabetes in man in which the sugar must be derived from proto- 

 plasmic metabolism. 



A puzzling feature is the absence of an increase of sugar in the blood ; if 

 the phloridzin is directly injected into one renal artery, sugar rapidly appears 

 in the secretion of that kidney ; the sugar is formed within the kidney cells 

 from some substance in the blood, but whether that substance is protein or 

 not is uncertain. The action of the kidney cells in forming sugar has been 

 compared to that of the mammary cells in forming lactose. 



Death in diabetic patients is usually preceded by deep coma, or uncon- 

 sciousness. Some poison must be produced that acts soporifically upon the 

 brain. The breath and urine of these patients smell strongly of acetone ; 

 hence the term acetoncemia. This apple-like smell should always suggest 

 the possible onset of coma and death, but it is quite certain that acetone 

 (which can certainly be detected in the urine) is not the true poison ; 

 ethyl-diacetic acid, which accompanies and is the source of the acetone, was 

 regarded by some as the actual poison ; but these substances, when intro- 

 duced into the circulation artificially, do not cause serious symptoms. The 

 principal poison is /3-hydroxybutyric acid or its amino derivative. The 

 alkalinity and carbonic acid of the blood are decreased, and the ammonia 

 of the urine is increased : this indicates an attempt of the body to neutralise 

 the poisonous acid. The acid is the source of the ethyl-diacetic acid and 

 of the acetone. Research has shown that /3-hydroxybutyric acid originates 

 in the body from fat. 



