William C. Stadie

FAT METABOLISM IN DIABETES MELLITUS

Excerpt The enormous amount of research on the abnormal metabolic processes of diabetes mellitus since the time of v. Mehring and Minkowski has failed to bring unity of conviction to students of th...

The Banting Memorial Lecture 1956: Recent Advances In Insulin Research

Dr. Ricketts, Members of the Association and Guests: I am indeed highly honored that this Society has selected me, one who long since abandoned the bedside for the laboratory, to give the Banting Lecture. I am happy to join with this Association to pay tribute to a great physician whose discovery of insulin has done so much to diminish suffering in man. Outstanding discoveries in the field of medical therapy are rare. We count surgical asepsis, anesthetics, and antibiotics among the important ones. The imperishable studies of Banting and Best added insulin to these. Its discovery generated problems in many areas of medicine and these have aroused the imagination and stimulated the activities of scientists all over the world. Driven by insatiable intellectual curiosity, they have labored indefatigably to search out the mode of action of insulin upon mammalian metabolism. Although obscurity still darkens the field, these researches reveal a pattern which begins to have meaning. I have undertaken the task in this hour to describe this pattern as I see it.

THE COMBINATION OF INSULIN WITH TISSUE

For some years past, the research activities of the Department of Research Medicine have centered around the question of the chemical action of insulin. This subject has excited the interest of many workers for more than seventy-five years and a t present is being actively pursued in many laboratories in a great variety of experimental ways. Recently, we have uncovered a new phenomenon, which we have termed “the combination of insulin with tissue.” We have performed many experiments to determine how significant this phenomenon is in the problem of the chemical action of insulin, and it is this work that I propose to discuss in this paper. The genesis of our work resulted from the emphasis which was given to homogeneous systems of enzymes in the study of the problems of intermediary metabolism. Systems of tissue extracts and substrates in simple aqueous solution were used. Great progress became possible by the successful isolation from such homogeneous systems of individual enzymes, many in crystalline form, and the demonstration of the specific chemical action which they, together with their coenzymes, catalyzed. By virtue of the great success of these methods, it became more or less axiomatic that complete understanding of metabolic pathways could not be achieved unless they were demonstrated in model or synthetic systems composed of highly purified enzymes. It was natural, therefore, to adopt the concept that the effect of hormones upon enzymatic systems could best be demonstrated in similar homogeneous systems which were free of intercellular boundaries or of cellular structures. Studies of the effect of hormones, particularly insulin, upon such homogeneous enzyme systems from normal and diabetic animals were reported in the literature, but an evaluation of this evidence, together with our own experiments, convinced us that there was no unequivocal evidence that insulin had any effect upon any enzyme system when it existed in cell-free or homogeneous systems. This brought us to the point where we were forced to reconsider the nature of the problem of insulin action. Accordingly, we formulated a new working hypothesis as the basis for further experimentation. This hypothesis consisted of two parts: (1) retention of cellular integrity is necessary for hormonal action upon enzyme systems (that is to say, the system, instead of being homogeneous, is heterogeneous) ; (2) the hormone itself must engage in the heterogeneity (this is another way of saying that the hormone combines with some receptor of cellular structure). Certain a prior; considerations made this hypothesis attractive : (1) the necessity of postulating a trimolecular reaction, a rare occurrence, among enzyme, hormone, and substrate would be eliminated; and (2) a combination of

Is The Metabolism of Peripheral Tissues Affected By The Arylsulfonylureas

Mr. Cowan is now eighty-nine and his wife eightyfour years of age. He is mentally alert and carries on a conversation concerning current events, as well as reminiscences regarding his long and interesting life. He has outlived his doctor and his allotted time of three score years and ten and credits his longevity to both insulin and an adequate diet. Mr. Cowans life should be an inspiration to all diabetic patients and a great satisfaction to the people still living who worked so diligently on insulin in the early days. He and his wife give daily thanks to those who saved his life and made it possible for him to live a normal, happy life.