The action of glucosone on normal animals (mice) and its possible significance in metabolism

Abstract

The almost simultaneous discovery by Emil Fischer (1) in Berlin and by Irvine, Fyfe and Hogg (2) at St. Andrews of the existence of reactive forms of sugars, coupled with the observations of Hewitt and Pryde (3) on the optical changes undergone by a sugar solution when introduced into a loop of living intestine, initiated the speculations of Winter and Smith (4, 5, 6) on the part played by the so-called “γ-glucose” in carbohydrate metabolism. The latter workers found that the optical activity and the copper-reducing power of a protein-free filtrate from normal blood were not compatible with the idea that the sugar present existed entirely as the ordinary equilibrium mixture of αβ-glucose. Having also observed that the fresh filtrate reduced potassium permanganate solution in the cold, they concluded that the glucose of normal blood exists in the unstable γ-form. Further, as the examination of the blood of diabetics pointed to their blood sugar being present as αβ-glucose, they suggested that the conversion of the relatively stable αβ-variety into the reactive γ-form was an essential step for utilisation of the sugar by the body cells and that this conversion was brought about by the action of insulin. These speculations unfortunately have not stood the test of later experiments (7, 8, 9), and though in 1923 Irvine (10), in the course of a review of the chemical evidence for the existence of a γ-form of glucose, pointed out the possibility that such a form may be produced in the body as an intermediary product during the glucose metabolism, he, in collaboration with Herring and Macleod (11), soon afterwards furnished experimental evidence against the theory of Winter and Smith, by showing that glucose monoacetone, a readily hydrolysable derivative of γ-glucose, is without action when administered in cases of insulin hypoglycæmia. More recently, however, the same idea, or one very similar, has been revived by Lundsgaard and Holboll (12, 13). They claim that when insulin and muscle tissue are added to a solution of ordinary a αβ-glucose, with a specific rotation of +52·5°, and the mixture incubated at 37°C., no change in reducing power takes place, but the optical rotatory value decreases to a new value varying from +15·9° to +42·2°, because of the formation of what they call “new” or “neo-glucose.” Insulin alone, or muscle tissue alone, does not produce the change, but the two factors, insulin and the active substance or principle in fresh finely minced muscle tissue, must act simultaneously (14).