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EDITORIAL FOCUS
Department of Physiology and Biophysics, University of Alabama Birmingham, Alabama
Professor Walter B. Cannon served as Chairman of the Department of Physiology at the Harvard Medical School for 36 years, from 1906 to 1942. His work centered on the sympathetic nervous system, gastrointestinal motility, traumatic shock, and the physiological basis of emotion. He authored numerous research articles as well as nine books. Cannon was extremely active in the American Physiological Society, serving as its sixth president. His service to the Society and to the discipline of physiology is commemorated by the Walter B. Cannon Physiology in Perspective Lectureship, the highest honor the Society bestows on an outstanding domestic or international physiological scientist and one that is cosponsored by the Grass Foundation. This lectureship was first presented in 1983 and has been given every year since that time.
Cannon wrote, in The Wisdom of the Body (3), that "The coordinated physiological processes which maintain most of the steady states in the organism are so complex and so peculiar to living beings... that I have suggested a special designation for these states, homeostasis."
He went on to say, "Organisms composed of material, which is characterized by the utmost inconsistency and unsteadiness, have somehow learned the methods of maintaining constancy and keeping steady in the presence of conditions which might reasonably be expected to prove profoundly disturbing." It is this principle of homeostasis that has driven generations of physiologists, indeed all life scientists, to probe in their research.
The work of the 2007 Cannon Lecturer certainly reflects and epitomizes Cannon's emphasis on the principle of homeostasis and in the application of varied experimental approaches to solve important biological problems. Professor Ashcroft's research interest, simply put, is to contribute to the understanding of glucose homeostasis. She approaches this broad question specifically through studying the molecular mechanisms of glucose sensing leading to insulin secretion. Professor Cannon himself was interested in blood glucose regulation. At an APS meeting in the early 20th century, he reported that a strong emotion, such as rage, produced a rise in blood glucose levels.
Dr. Ashcroft's work has shed new light on fundamental mechanisms of the physiological regulation of insulin secretion in both health and disease. She published a seminal article in 1984 in Nature (2), showing that glucose inhibited potassium currents in pancreatic 
-cells. Her subsequent work established this potassium channel as an ATP-sensitive channel, and her group has provided ample mechanistic insight into the way this K channel associates with the sulfonylurea receptor to form a fully functional channel. Importantly, she showed that this channel acts as the key link between blood glucose concentration and insulin secretion. Since these seminal discoveries, Professor Ashcroft has been in the forefront of the electrophysiological characterization of this important K channel and the physiological role this channel plays in -cell function. Recently, Dr. Ashcroft discovered, through a combination of mutagenesis, analysis of human genetic diseases, homology modeling, and direct structural analysis of purified channels, that the ATP binding site is on the K channel protein itself.
This finding has altered the clinical view of neonatal diabetes. Instead of this disease being categorized, as it was, as an autoimmune disease, Ashcroft and her group found that babies with this disease carry gain-of-function mutations in the K channel gene, leading to hyperpolarized pancreatic -cells and nonresponsiveness to blood glucose levels. This finding immediately led to a change in the treatment protocol, with a resulting significant attenuation of morbidity. This is an example of translational research at its finest! This body of work, summarized in the accompanying article (1), demonstrates unequivocally how a full understanding of the molecular basis of ion channel dysfunction can lead to better disease management.
REFERENCES
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