230 IV. CONVERSION OF FAT TO CARBOHYDRATE 



the epinephrine experiments, since the negative results explain and far out- 

 weigh the positive ones. 



(4) The Importance of Insulin 



Shortly after the discovery of insulin, Wertheimer'-^ postulated that this 

 hormone facilitates the conversion of fat to sugar. This hypothesis seemed 

 logical at the time it was proposed, since it had been demonstrated that the 

 deposition of liver glycogen occurred in the diabetic animal following in- 

 sulin treatment, concomitantly with a decrease in blood sugar, urine sugar, 

 and blood and liver fat.^-- In Wertheimer's experiments, it was noted that 

 glycogen appeared in the livers of phlorhizinized dogs after the injection of 

 insulin, practically simultaneously with the disappearance of excess fat. 

 Another fact which tended to support this conclusion was the observation 

 that dogs with fatty livers were more resistant to insulin, and that the 

 blood sugar returned to normal more quickly after insulin injection than in 

 control animals with lower fat stores. However, these results are refuted by 

 Hawley,^"* who states that "even when there was a very great need of carbo- 

 hydrate to save the life of the animal, and when there were ample stores of 

 fat or ample food fat available to meet this need, there was no gluconeo- 

 genesis from fat." 



(5) Experimental Data from Isolated Organs 



a. Fat Change and Carbohydrate Content. A number of reports based 

 upon quantitative studies of carbohydrate synthesis by perfused or isolated 

 tissues indicate that fat is converted to carbohydrate. As a result of per- 

 fusion studies with isolated livers and with minced livers from normal and 

 diabetic animals, a number of workers^-^"^-^ postulated the origin of car- 

 bohydrate from fat in this organ. In these tests, more carbohydrate was 

 formed than could be accounted for by the decrease in known precursors of 

 this foodstuff. ^"^ However, Gregg^-^ was unable to confirm these experi- 

 ments. He concluded that, in order to establish a conversion of fat to car- 

 bohydrate in the liver by the use of the balance technic, it would be neces- 



121 E. Wertheimer, Arch. ges. Physiol. (Pfluger's), 213, 298-320 (1926). 

 1^* J. J. R. Macleod, Carbohydrate Metabolism and Insidin, Longmans Green, London, 

 1926, pp. 104, 163, ff. 



1" H. Heller, Acta Med. Scand., 90, 489-526 (1936). 



12* J. Seegen, Arch. ges. Physiol. {Pfluger's), 39, 132-142 (1886). 



125 J. H. Burn and H. P. Marks, J. Physiol., 61, 497-517 (1926). 



126 H. Jost, Z. physiol. Chem., 197, 90-134 (1931). 



127 L. Lattes, Biochem. Z., 20, 215-219 (1909). 



128 D. E. Gregg, Am. J. Physiol, 103, 79-88 (1933). 



