Since its landmark discovery in 1922, insulin has improved the health and extended the lives of more than 500 million people worldwide with diabetes mellitus. Yet the question of how this key hormone binds to its target cells in the body’s organs has posed an enduring scientific mystery. A global team of researchers from Cleveland, Australia, Chicago, India and Oregon has made a discovery about insulin and its structure that promises to enable design of new insulin products that will do a better job of regulating the metabolism of patients with diabetes. The scientists, co-led by Michael A. Weiss, MD, PhD (Case Western Reserve School of Medicine, Cleveland) and Michael C. Lawrence, PhD (Walter and Eliza Hall Institute and the University of Melbourne, Australia), deciphered how the insulin molecule exploits a “protective hinge” to engage its primary binding site within the insulin receptor. The results of the team’s interdisciplinary research appeared the first week of August in an online edition of PNAS (Proceedings of the National Academy of Sciences). Solving this problem required integration of synthetic, biochemical, biological, spectroscopic and crystallographic approaches. “We discovered an essential mechanism for how insulin binds to target cells and thereby triggers an extraordinary cascade of
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