Exercise and the stress axis: Implications for the development of type 2 diabetes mellitus

Abstract

Dr. Mladen Vranic's scientific contributions in the areas of exercise and stress physiology began at the University of Zagreb in the late 1950s. Some of this seminal work described the effects of prolonged fasting on glycemic regulation in normal and adrenalectomized rats ( 1. Vranic M. Pokrajac N. The effect of age and fasting on blood sugar level in normal and adrenalectomized rats. J Gerontol. 1961; 16: 110-113 Crossref PubMed Scopus (7) Google Scholar ). Interestingly, this early work illustrated that the adrenal glands in rats contributed markedly to elevations in blood glucose (BG) during fasting, particularly in older rats. This work foreshadowed his later investigations into the role of stress in promoting hyperglycemia in animal models of both type 1 and type 2 diabetes mellitus. Similar to what the famous Austro-Hungarian scientist Hans Selye (1907–1982) had been reporting, it was clear that the adrenal glands were activated during a stress response which, in turn, would increase BG levels—a major concern for those with diabetes. As was reported in that paper by Vranic and Pokrajac ( 1. Vranic M. Pokrajac N. The effect of age and fasting on blood sugar level in normal and adrenalectomized rats. J Gerontol. 1961; 16: 110-113 Crossref PubMed Scopus (7) Google Scholar ), the older rats would have less capacity to deal with the stress of fasting, since their capacity for glucose disposal was somewhat compromised. This research set the stage for the subsequent half-century of research on diabetes metabolism.