The Effect of Experimental Obesity upon Carbohydrate Metabolism *

The hypothalamus has been accepted by many investigators as an important center for the regulation of carbohydrate metabolism in the same way that medullary centers control respiration. Evidence for this point of view, however, is inconclusive and controversial (see Long"2) except for the well-confirmed transient hyperglycemia and glycosuria which follow hypothalamic stimulation or damage (Aschner,1 Himwich and Keller7). Houssay and Biasotti8' 9, 10 reported alleviation of pancreatic diabetes by lesions placed in the tuberal portion of the brain-stem of the toad. In the dog, however, similar lesions had no such effect. Amelioration of pancreatic diabetes was later descrilbed by Davis, Cleveland, and Ingram5 in cats with hypothalamic lesions. The mechanism of production of this effect was not specified, but it was assumed to have been due to interruption of the nerve supply or interference with the blood supply of the anterior lobe of the hypophysis. Their conclusions have been widely quoted in both experimental and clinical literature, but apparently their data have not been confirmed. The effect of experimental hypothalamic lesions upon carbohydrate metabolism has now been studied in albino rats prepared in one of three ways: (1) An attempt was made to confirm the results of Davis, Cleveland, and Ingram5 by producing bilateral hypothalamic lesions in rats which were frankly diabetic as the result of partial pancreatectomy. At the time of hypothalamic operation the glycosuria of each of the rats was quantitatively well stabilized; the effect of the operation, therefore, could easily be determined. (2) The well-known frequency of association of clinical obesity with diabetes mellitus led also to an attempt to study this association in the rat. Partially pancreatectomized rats which had no spontaneous glycosuria were subjected to hypothalamic lesions of the type which produces hyperphagia and obesity ((Brobeck et al.3). In this way it