C. H. BEST 



physiological mechanism for the increased or decreased rate of libera- 

 tion of insulin in the severe diabetic permits wider fluctuations from 

 the normal range of values. 



The detailed mechanism of the action of insulin is by no means 

 as clear as its specific effect on the diabetic state might suggest. It 

 was soon learned that the formation of the key polysaccharide — 

 glycogen — was stimulated by insulin and that the burning of sugar 

 was increased. The extremely wasteful and very dangerous break- 

 down of proteins to sugar and of fat to ketone bodies in the liver is 

 checked by insulin. The formation of fat from sugar is accelerated; 

 and there is some evidence that certain of the phosphate compounds 

 of paramount importance in the provision of energy for muscular 

 contraction may be regenerated at a greater rate when insulin is 

 present. Some workers believe that the amount of adenosine tri- 

 phosphate in the liver is increased by the action of insulin. 



A very great deal has been learned in recent years which adds 

 to our understanding of the pathway of carbohydrate storage and 

 breakdown in the body. It would appear that most, if not all, of these 

 steps may be traversed without the action of insulin, but our knowledge 

 of these processes is not complete. A great step forward is represented 

 by the recent demonstration by Cori et al. that insulin releases the in- 

 hibition of the conversion of glucose to glucose-6-phosphate, which is 

 exerted by anterior pituitary extract. 



While in a diabetic animal deposition of glycogen in both liver 

 and muscle is greatly increased by insulin, in the normal animal muscle 

 appears to have a "higher priority" and deposition of glycogen in this 

 tissue, after insulin administration, may be accompanied by a fall in 

 glycogen content of liver. 



We have a great deal more to learn concerning the best estab- 

 lished effect of insulin, i. e., the promotion of glycogen deposition, and 

 we have even more to learn about the mechanism by which the break- 

 down of protein and fat is inhibited. It is possible that insulin in 

 some way controls the substrate which is presented to the tissue cells 

 for metabolism. 



The intelligent use of such labeling agents as radioactive phos- 

 phorus and the stable isotopes of carbon, nitrogen, sulfur, and other 

 elements is certain to illuminate many of the dark passages through 

 which insulin passes in producing its effect on diabetes. We can 



428 



