Holloszy, John O.A forty-year memoir of research on the regulation of glucose transport into muscle. Am J Physiol Endocrinol Metab 284: E453-E467, 2003; 10.1152/ajpendo.00463.2002.-This historical review describes the research on the regulation of glucose transport in skeletal muscle conducted in my laboratory and in collaboration with a number of colleagues in other laboratories. This research includes studies of stimulation of glucose transport, GLUT4 translocation, and GLUT4 expression by exercise/muscle contractions, the role of Ca 2ϩ in these processes, and the interactions between the effects of exercise and insulin. Among the last are the additive effects of insulin and contractions on glucose transport and GLUT4 translocation and the increases in muscle insulin sensitivity and responsiveness induced by exercise.MY FRIEND, MIKE MUECKLER, in his role as Editor of the American Journal of Physiology-Endocrinology and Metabolism, asked me to write this review in the form of a memoir describing my research on glucose transport and metabolism in muscle. As this is a personal history rather than a general review, I hope that my colleagues working in this area will forgive me for focusing primarily on the work of my laboratory. There are a number of broad reviews of this area available (17,35,54,65,69,117,122,134).
HOW IT BEGANDuring medical school and specialty training in internal medicine and endocrinology/metabolism, I became interested in the concept that the chronic metabolic diseases of advancing age, atherosclerosis, type 2 diabetes, and hypertension, are largely due to lifestyle and environmental factors and, therefore, to a considerable extent, preventable. In addition to the evidence regarding the role of diet, studies by Jeremy Morris and others comparing physically active and inactive people suggested that exercise deficiency might be playing a role. As a consequence of my interest in the role of exercise deficiency in the development of coronary atherosclerosis, I was recruited by the Heart Disease Control Program of the United States Public Health Service (USPHS) in 1961 and stationed at Dr. Tom Cureton's Physical Fitness Research Laboratory at the University of Illinois. Tom Cureton was a pioneer in the area of endurance exercise training, and he and his graduate students conducted a noon hour exercise program for middle-aged university faculty and Champaign-Urbana businessmen.My assignment was to organize and conduct studies on the effects of the exercise program on risk factors and heart function. These studies were conducted with the help of Jim Skinner, who was one of Cureton's graduate students, and other members of the Fitness Research Laboratory. We found that exercise lowered serum triglycerides and improved heart function (70,71,118). However, what really fascinated me was the remarkable and rapid improvement in exercise capacity and endurance that occurred in response to the exercise training. This phenomenon so intrigued me that I decided to investigate the underlying biological mechani...