540 THE LIVER [CH. XXXV. 



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. Possibly it is 

 here that the internal secretion of the pancreas comes in. 



Cohnheim discovered that muscle by itself and that an extract of 

 pancreas by itself have very little effect in destroying sugar at body 

 temperature; but if a mixture is made of surviving muscle, pan- 

 creatic extract, and sugar, the last-named substance rapidly dis- 

 appears. Several observers have confirmed this observation, but 

 others attribute it to bacterial action ; according to this view, the 

 pancreas forms a substance which activates the glycolytic (sugar- 

 destroying) enzyme of muscular tissue. The activating substance 

 is not an enzyme, because the pancreatic extract does not lose this 

 property when it is boiled. 



Levene, like others, finds that sugar disappears when mixed with muscle and 

 pancreatic extract, but he does not regard this as glycolysis in the usual accepta- 

 tion of the word, namely, combustion into carbonic acid and water. He considers 

 that the sugar disappears because its molecules are condensed into a heavier 

 carbohydrate, and states that the sugar can once more be recovered from the 

 mixture after hydrolysis with acid. If this is confirmed the view above advanced 

 will need revision, and the action of the pancreatic hormone is best explained, as 

 suggested on the next page, as antagonistic to that of adrenaline. Of all the tissue 

 cells examined by Levene, the leucocytes alone were found to possess real 

 glycolytic power, lactic acid being an intermediate stage before the final products 

 (carbonic acid and water) are reached. 



(3) By administration of phloridzin. Many drugs produce 

 temporary glycosuria; some, such as morphine, may act on the 

 diabetic nerve-centre; others, such as anaesthetics and carbon 

 monoxide, may upset the balance between the blood-gases, and thus 

 affect tissue respiration and lead to an accumulation of sugar in the 

 blood. The most potent poison in producing a diabetic state is, 

 however, phloridzin, which is a glucoside, but the sugar passed in the 

 urine is far 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 protein metabolism. The increase in 

 protein metabolism is signalised by the rise in the output of nitrogen ; 

 in these cases the ratio of dextrose to nitrogen in the urine is 3'6 : 1. 

 If such a ratio occurs in man on a diet free from carbohydrates, a 

 serious condition is revealed ; Graham Lusk calls it the " fatal ratio." 



A puzzling feature is the absence of an increase of free sugar in 



