248 1. lODOACETATE AND lODOACETAMIDE 



companying tabulation). This would harmonize with the results of Haar- 

 mann (1932), who showed that bromoacetate has no effect on glycogenolysis, 

 but reduces glucose utilization; hyperglycemia on tliis basis would be due 



Time (min) Blood glucose (mg%) 



to a reduced rate of glucose utilization. Hikiji (1932) showed that there is 

 a rather marked loss of muscle glycogen following injection of 20-40 mg/kg 

 bromoacetate. It is possible that some of the blood glucose originates from 

 this glycogen. Irving (1934) pointed out that hyperglycemia is seen only 

 when lethal or near-lethal doses of iodoacetate are given, although the 

 mortality does not depend on the hyperglycemia, since insulin will counter- 

 act the hyperglycemia without protecting the animal. Subcutaneous doses 

 of iodoacetate (80 mg/kg) in starved rabbits lead to a rise in blood glucose 

 from 125 mg% to 210 mg% in 40 min. Irving tended to believe that the 

 reduction in the tissue utilization of glucose is the principal factor in caus- 

 ing the hyperglycemia. Definite hyperglycemia was also reported by Hand- 

 ler (1945), who found 180% increase of blood glucose after 71 mg/kg iodo- 

 acetate injected into rabbits, and El Hawary (1955), who fovmd a 2-fold 

 increase after 75 mg/kg iodoacetate intraperitoneally into rats. On the 

 other hand, hypoglycemic responses have also been encountered. Rex-Kiss 

 and Zsadon (1939) observed only decreases of 10-35% in the blood glucose 

 in dogs given 10-25 mg/kg iodoacetate intravenously, and Hultquist (1958) 

 reported around 20% depressions of blood glucose from 50 mg/kg iodoace- 

 tate or 30 mg/kg iodoacetamide subcutaneously in rats, no hyperglycemia 

 being noted at any time. The last two reports deal with rather low doses of 

 iodoacetate, while those who found hyperglycemia generally used lethal or 

 near-lethal doses. Unfortunately no complete study of the dosage range in 

 any animal has been made, so it is impossible to relate these discrepant 

 results entirely to dosage, as many other factors may be involved. 



Blood glucose level depends on the balance between the rates of a few 

 transport processes, mainly the absorption from the intestine, the excretion 

 by the kidney, and the transfers in and out of the other tissues (Fig. 1-26). 

 The effects of iodoacetate may well depend on whether the animals have 

 been starved or not, since glucose absorption through the intestine is inhib- 

 ited by iodoacetate (Wilbrandt and Laszt, 1933; Klinghoffer, 1938; OhneU 

 and Hober, 1939; Laszt, 1939). If glucose absorption is an important factor 



