VOL. 12 (1953) BIOCHIMICA ET BIOPHYSICA ACTA 329 



EFFECTS OF INSULIN ON MELANOMA AND BRAIN METABOLISM 



by 



MARK WOODS, KENT WIGHT, JEHU HUNTER and DEAN BURK 



National Cancer Institute, National Institutes of Health, 



Public Health Service, Department of Health, Education and Welfare 



Bethesda, Maryland (U.S.A.) 



INTRODUCTION 



The prime importance of glycolysis in the metabolism of tumors was first recognized 

 in the researches of Otto Warburg begun over 30 years ago. In 1930^^ he wrote, in 

 summary, "Glycolysis is a property of all tumors, and very different types of tumors 

 agree quantitatively, as regards gl5/colysis, to a considerable extent." Today, as the 

 result of his continued researches and those of many others, Warburg has reaffirmed 

 that "shifting of the metabolism to the anaerobic state is the main biochemical difference 

 between the tumor and normal cell"^^. 



Since the primary known action of insulin is a stimulation of glucose uptake, and 

 associated processes, the possible role of this hormone in tumor glycolysis is of special 

 importance, particularly since tumors are geared to a glucose metabolism. While there 

 is a considerable literature dealing with the effect of insulin on the in vitro metabolism 

 of normal tissues, relatively little has been reported concerning its in vitro action on the 

 metabolism of malignant tissues. In the present paper we report metabolic responses 

 obtained following direct addition of insulin to reaction vessels containing freshly 

 sectioned tissue. Such an approach has the advantage of exposing the tissue in question 

 to the direct action of the hormone and related substances {e.g. zinc). Our studies have 

 been limited chiefly to the malignant S-91 mouse melanoma of Cloudman^, and to 

 whole brain preparations of normal mouse. Brain was compared with melanoma because 

 both tissues possess a marked glucose metabolism ; both display a considerable aerobic 

 glycolysis; and, although the tumor melanoblast cannot be considered a nerve cell 

 per se, it is in all probability of neural origin^^'^^. The results obtained with brain do not 

 demonstrate positive effects of added insulin but they do illustrate significant metabolic 

 differences between the two types of tissues. The results with melanoma indicate that 

 insulin plays an important role in determining the rate of glycolysis {Qco^, Qco) ^.s well 

 as influencing certain other metabolic functions. Furthermore, the data from these 

 in vitro experiments indicate that zinc plays a critical role in insulin action. 



MATERIALS AND METHODS 



The S-91 melanoma was maintained by intramuscular transplantation in dba mice as previously 

 described^'', and was actively growing and readily transplantable*. Normal brains were usually 



* The authors are indebted to Mr George Hobby for his valuable assistance in maintaining the- 

 tumors used in this investigation. 



References p. 346. 



