Orchestration of Glucose Homeostasis

From a Small Acorn to the California Oak

  1. Richard N. Bergman
  1. From the Keck School of Medicine, University of Southern California, Los Angeles, California
  1. Address correspondence and reprint requests to Richard N. Bergman, PhD, Keck Professor of Medicine, and Chair, Department of Physiology and Biophysics, Keck School of Medicine, MMR626, 1333 San Pablo St., Los Angeles, CA 90033. E-mail: rbergman{at}usc.edu

Type 2 diabetes is increasing at alarming rates in the U.S., in Westernized countries, and in the third world. The increasing costs in terms of human suffering as well as economics are well recognized (1). Improved understanding of the pathogenesis of diabetes should lead to better approaches to predict, forestall, or even prevent diabetes and to treat extant cases. Yet, the precise causes of this disease remain to be totally explained. There is little question that obesity per se is a primary contributor, but the causes of the so-called “obesity epidemic” are in debate (2), as are the mechanisms by which obesity itself is linked to diabetes (3,4).

For some years, our laboratory has been engaged in efforts to understand causation of type 2 diabetes in terms of insulin secretion and resistance and to attempt to account for the role of obesity. The Banting Lecture provided me with a rare opportunity to describe our research efforts done over a prolonged history in a single presentation. It was my goal to address the several areas of diabetes research we have done. At first glance these different areas may appear unrelated. But these lines of work are closely linked within an overall effort to understand diabetes. I am deeply grateful to the members of the American Diabetes Association for the great privilege of making this presentation. I hope I will be able to emphasize the wonderful opportunity that I and my colleagues have had to pursue original research in a highly deserving and important cause. One can scarcely ask for more in one's professional life.

For several decades it has been popular to pursue a “reductionist” approach to studying disease (Fig. 1). The underlying concept is that understanding of disease will result from describing events at increasingly more microscopic …

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