CHAPTER 4 



ALLOXAN 



Alloxan is an unstable SH reagent which reacts readily with certain 

 thiols but not with most protein or enzyme SH groups. It is thus not a 

 reliable SH titrator but exerts inhibitions of interest and, like iodoacetate 

 and iV-ethylmaleimide, is a valuable tool because of its* selectivity. The 

 modern interest in alloxan stems from the observation of Dunn and his 

 associates (1943 a) in Glasgow that it can produce specific pancreatic 

 islet necrosis in rabbits. This had been observed in their laboratories as 

 far back as 1926, in studying renal lesions induced by urate and related 

 compounds, but had not been published. Jacobs (1937) had indeed reported 

 that alloxan exerts profound effects on blood glucose levels, but had ob- 

 served only the early hypoglycemia and did not study the animals suf- 

 ficiently long to note the development of the later diabetic hyperglycemia. 

 Dunn and his group also did not observe the animals long enough to char- 

 acterize the diabetes produced as the result of islet destruction, but the 

 occurrence of typical diabetes was reported by Brunschwig et al. (1943) 

 and Goldner and Gomori (1943) in Chicago, and a month later independently 

 by Bailey and Bailey (1943) in Boston. It was by now clear that damage 

 to the islet tissue is confined to the insulin-secreting /5-cells, the a-cells 

 being resistant to alloxan, and this diiferential action was demonstrated 

 particularly well by Dunn et al. (1944). These results provided an easy and 

 specific method for inducing experimental diabetes in animals and this 

 has contributed greatly to the study of diabetes. In addition, it has posed 

 the very fascinating problems of the selective action of alloxan on a single 

 type of cell and the mechanism by which alloxan initiates within a few 

 minutes the progressive destruction of these cells. On the tissue level al- 

 loxan is one of the most selective inhibitors known. 



At the time of the discovery of its diabetogenic action, alloxan had been 

 known for over a century, but only sporadic reports on its biological ef- 

 fects had appeared. It was synthesized by Wohler (1838), its reactions 

 with amino acids were studied by Strecker (1862), the possibility of its 

 natural occurrence in animals was indicated by von Liebig (1962), Lang 

 (1866) and Ascoh and Izar (1909), and its reactions with SH groups were 



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