Effect of Dinitrophenol on Experimental Diabetes

Abstract

The metabolic action of 2-4-dinitrophenol has been the subject of several recent and informative studies. Thus the greatly increased oxygen consumption characteristic of its administration to animals and man seems from the observations of Hall, Tainter, Cutting and coworkers 1 , 2 to be largely at the expense of fat as a fuel, at least when the stimulus augmenting metabolism is not too abrupt and overwhelming. There is general agreement that dinitrophenol does not increase the output of nitrogen in the urine^1-5 and hence protein catabolism seems to be little affected. The injection of large and generally fatal doses into animals causes some elevation of the blood sugar and a considerable loss of liver and muscle glycogen, but smaller doses have little effect on the blood sugar. 2 ,⁶,⁷ The glycemic effect of large doses of dinitrophenol is not dependent upon asphyxia⁸ and examination of the blood shows no very significant shift in the acid-base balance. 2 ,⁸,⁹ Studies of the ammonia, organic acid and ketone body excretion of patients administered dinitrophenol indicate that the increased oxidation of fat is complete. 1 , 3 , 4 In fact, as Tainter, Cutting, and Hines 1 have stated the salient feature in the study of dinitrophenol is the negative findings in so many phases of its metabolic action.

The administration of a different oxidative stimulant, thyroid extract, to partially depancreatized dogs results in a severe and even fatal diabetes,¹⁰,¹¹ and similarly, thyroid medication, or the spontaneous occurrence of hyperthyroidism, greatly increases the severity of human diabetes, inhibiting the action of insulin and often precipitating ketosis.¹² In the past the generally accepted explanation of the adverse effect of hyperthyroidism on diabetes mellitus has been that advanced by Wilder,¹² namely that with the important exception of exercise, “measures or conditions which stimulate the general metabolism have a depressing action on the tolerance of the diabetic patient.”