THE RELATION OF THE PANCREAS TO DIABETES
JOSEPH H. PRATT
1910
Journal of the American Medical Association (JAMA)
absolute alcohol and long exposed to the action of light, does undergo a reduction to beta-oxybutyric acid, while the alcohol hums to acetaldehyd. Magnus-Levy and others have leaned to the view thai aceto-acetic acid, when formed in ihe body, is deslroved by a direct acid splitting into two molecules of acetic aid, which then oxidize fur¬ ther; whereas, if we assumed that the bodily destruction of aceto-acetic acid produced in accordance with the mechanism of Ciamician and Silbcr's reaction, we
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... would tlien have to consider thai acèto-acetic acid is destroyed by reduction, not splitting followed by oxidation. Is Ibero any evidence to support such a conception? As al ready stated, the Italian writers found that tro-bodies, like ketones. underwent reduction under the conditions in question. Nilrobenzol, for example, is reduced by alcohol to anilin, according to the general rule. Now, nilrobenzol, when ingested by men or ani¬ mals, undergoes in the body reduction to para-aminophenol, a near derivation of anilin and one which occurs in the urine when anilin itself is ingested. Outside the body the reduction depends on simultaneous oxidation of alcohol groups. Is it so dependent in the body? If so, animals in which sugar oxidation is virtually eliminated by the use of phlorhizin and abstinence from food should be unable to reduce nilrobenzol to nara-aniiiio-phennl. This appears to be the case. Recently Dakin,4 Freedniann and Masse Blum" have shown that actetoacetic ¡u-id when intravenously injected (as a solu¬ tion of the sodium sail) into dogs and cats is actually reduced to beta-oxybutyric acid, whereas it is well known thai in acidosis very considerable amounts of aceto-acetic ¡u-id may be spontaneously introduced into the blood¬ stream without the appearance of beta-oxybutyric acid in the urine. In favor of the idea that aceto-acetic acid is normally destroyed by reduction in the course of a sim¬ ultaneous oxidation and reductive reaction like those exploited by Ciamician and Sillier, (here is the following condensed evidence: Aceto-acetic ¡u-id in the presence of an alcohol outside the body is reduced, the alcohol under¬ going simultaneous oxidation. Aceto-acetic acid is reduced in the body when sugar (alcohol) oxidation is going on (Dakin el al.). When sugar oxidation fails aceto-acetic acid is spontaneously excreted in large amounts, and moderate amounts of aceto-acetic acid may exisl prior lo the appearance of any beta-oxybutyric ¡u-id in the urine. Nitro-bodies, which act outside the 'body in the same general way as aceto-acetic acid and olher ketones, are also reduced in the healthy body, hut when sugar oxidation is eliminated they. too. apparently fail to be reduced. In every case the substances which destroy acidosis in the body also reduce ketones, nitrobodies. etc., in the sunlight. Reduction of aceto-acetic acid will account for the dis¬ appearance of Ibis substance and ils splitting product acetone, i. e., two of the acetone bodies. It must now be asked what becomes of the beta-oxvbul vric acid which is fol med in the process. Then» is always the possibility thai beta-oxybutyric acid can be oxidized in the body in two différent ways. If so, then in health one would conci ive of a double oxidation of beta-oxybutyric acid, two products being formed, aceto-acetic acid on the one hand and a dioxybutyric acid on the other. The hitler sub¬ stance, being easily oxidizable. would rapidly burn furl her. The aceto-acetic acid as fast as formed would be reduced back again into beta-oxybutyric acid. In this way all beta-oxybutyric acid would eventually have to oxidize over the dioxybutyric route, this being the only way in which it could oxidize and stay oxidized. Note.-One might think here ot n sort of organic chemical equilllii'iiiin between molecules of. say. beln-oxylinlyi-ie ¡u-id and those dis¬ sociation products thereof whose existence ¡s the prelude to formation of nlplin and alpha-beta ox.varids respectively, such equilibrium being comparable io tbat which exisis in ¡i solution of ¡in electrolyte between the molecules of tin-electrolyte and its ions as expressed for NaCl liy the familiar formula Na X CI -=K. NaCl If Un-prbporl innate con¬ clu rations of beta particles becomes lessened by a rapid excretion of aceto-acetic acid InBtead of being maintained by constant reduc¬ tions of tin» same tin-equilibrium would become disturbed and in tinattempt to maintain it a very high aggregate amount of beta products would in» formed ¡uni a very low aggregate of alpha-beta products. Normally tbe entire balance may be reversed in simple accordance with tbe laws of mass notion. 4. Dakin. H. D.: A New Mode for the Formation of Beta\x=req-\
doi:10.1001/jama.1910.04330250008004
fatcat:pdlxcofsifhw3c3vsno53tgbna