:393 Newer Concepts of the Action of Insulin

S INCE the discovery of insulin, thousands of research workers have concerned them-selves with experiments designed to show the metabolic defect in diabetic organisms and the mode of action of insulin upon mammalian metabolism. The problem is still obscure but a pattern begins to reveal itself and in this brief discussion I shall undertake to describe this pattern as I see it. Many hypotheses have beemi formulated to explain why the early steps in the mnetabolismn of glucose are impaired in diabetes. The possible role of the cell membrane was neglected until in 1927, proposed a “membrane theory of dia-betes. ‘ ‘ He called attention to the possibility that certain pathologic relationships in cellular metabolism might be due to disturbances of normal permeability of cells. He said: “One thinks that an abnormal constitution of the cell membramie (perhaps of the liver cell) does not allow the simple sugars to reach their normal focus of breakdown. If one considers the above possibility it is possible to substi-tute for the present theory of diabetes, which is based upon concepts of abnormal enzymatic activities, another viewpoint: the membrane theory of diabetes. ” Hoeber himself presented no experimental data to support this hypothe-sis and some 25 years passed before two investi-gators, Levine ’ of Chicago and Ross3 of Lon-domm studied the possible role of permeability fac-tors in diabetes, each approaching the subject from different points of view. Levine selected the eviscerated dog as the experimental 1re1-aration for study. He selected sugars, for example galactose, which were essentiall