DEWITT STETTEN, JR. 



more frequent than defects in its sources and generation. Where- 

 as all tissues in the mammal, so far as is known, are capable of 

 assimilating glucose, attention has been directed largely to the 

 liver and to the skeletal musculature. Although wide fluctuations 

 in glucose utilization may be induced in these tissues by altera- 

 tion of the hormonal or nutritional state, certain other tissues, 

 e.g., brain, myocardium, fetus, appear to be insulated against 

 drastic changes in rate of glucose consumption. Thus whereas 

 the liver or muscle is sensitive to the concentration of circulating 

 insulin, brain is not, although it obviously cannot tolerate 

 extremes of hypoglycemia. 



The rate of assimilation of glucose by muscle is critically 

 dependent upon the activity of the islets of Langerhans, the 

 anterior pituitary gland, and possibly also the adrenal cortex. 

 Space does not permit an analysis at this time of the various 

 conflicting lines of evidence relating to the exact sites of action 

 of the several participating hormones. For purposes of the 

 present discussion it matters little whether the role of insulin is 

 to release muscle hexokinase from a physiological inhibition (16) 

 or to facilitate the entry of unesterified glucose from the extra- 

 cellular space into the intracellular compartment of muscle (9). 

 It will suffice, for the present argument, to select the area of 

 agreement between the conflicting experiments and define the 

 net result of insulin action as increasing the quantity of intra- 

 cellular glucose-6-phosphate at the expense of extracellular, 

 ultimately plasma, glucose. Similarly we need not concern 

 ourselves too much, at this time, with the question of whether 

 the anterior pituitary gland secretes an agent that directly 

 inhibits hexokinase (16) or whether it interferes in some fashion 

 with the operation of insulin which is bound to muscle (18). 

 Growth hormone, or some biological product derived therefrom, 

 appears to render muscle insensitive to the action of insulin in the 

 intact animal. 



Again in the intact animal the situation is complicated by 

 the fact that, in addition to influencing what is happening in mus- 

 cle, each endocrine may exert influences upon other endocrine 



170 



