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V H - INVESTIGATION OF GLUCOSE METABOLISM AND ITS RELATION TO MENTAL FUNCTION AND GANGER THEBAFT 1 j w 1 3$ It is well known that the brain in its metabolic function relies heavily’ on glucose and o^gen. The importance, of the relation of glucose to cerebral function eras first emphasized by the introduction of ihsulin shock therapy- into the treatment of schizophrenia. This foral,of shock therapy was subsequently replaced by electric shock, but recently dHMflMhHMNfcof 3 MHHBbhas shown that in diabetics the psychotic state can be induced by low blood sugar in the brain from sensitivity to insulin and can be reversed to normal by the intravenous administration, of glucose. . The author has been interested in substituting orally active and nontoxic chemical compounds as a substitute for insulin with, the hope that more simple methods can be devised for modifying cerebral metabolism. A series of alkyl and alkylamino esters of oxy-diacetic acid have been prepared which block some phase of the Kreb's cycle of glucose metabolism. The exact point of blockage remains to be determined. The phenomena of blockage by these compounds, however, have been demonstrated in ' animals by showing that they produce glycogen storage in the liver, heart, and kidneys by preventing the conversion of glycogen to glucose. For the first time it has been possible to produce experimentally von Gierke's disease, which is characterized by glycogen — . . storage in tbe above-mentioned organs.- .. The phenomenon of glycogen storage was first produced by both die dimethyl and diethyl derivatives of the diglycolate compounds. The initial experiments consisted of giving groups of six rats each doses of 5, 10, and 2S mg. per rat daily for periods of 6 weeks to 2 months. The glycogen storage was most marked early in the course of the administration, as demonstrated by sacrificing some rats at the end of 2 to 4 days. The experiments were subsequently modified to include rabbits, so that the blood »nd urine studies could be more easily made. It was shown in rabbits that the compounds initially