Michael Weiss, MD-PhD, Publishes Fundamental Insights into Overcoming Insulin’s Limitations
Indianapolis, IN, November 5, 2020 – Thermalin co-founder Dr. Michael Weiss, Distinguished Professor at the Indiana University School of Medicine, published today a major insight into the evolutionary basis of the Type 2 diabetes mellitus: “Evolution of insulin at the edge of foldability and its medical implications.”
Leading an interdisciplinary team at IU, the University of Michigan and Case Western Reserve University, Dr. Weiss discovered that the insulin gene in mammals (including in humans) has become entrenched in an evolutionary “cul-de-sac.” The many competing structural requirements that insulin must satisfy–from biosynthesis and storage to secretion and hormone action–has frozen its amino-acid sequence at the edge of toxic misfolding. Ordinarily the limits of foldability would not be encountered, but in the face of over-nutrition and sedentary life styles, the line of toxic misfolding is crossed, leading to chronic stress in pancreatic beta-cells, the body’s factory for making insulin. As described in the Proceedings of the National Academy of Sciences (PNAS), the genetic history of the insulin gene thus provides an evolutionary backdrop to “diabesity” as a pandemic disease of civilization. This discovery suggests a new avenue to prevent or treat T2D focused on the pathway of beta-cell stress.
“This study is a tour de force unraveling key elements of the structural biology of insulin that affect its synthesis and function,” said Barbara Kahn, MD, George R. Minot Professor of Medicine at Harvard Medical School. “The authors highlight the fact that the insulin gene has been susceptible throughout evolution to mutations that impair insulin’s function or stress beta cells. As we approach the 100th anniversary of the discovery of insulin, these elegant observations might lead to a better understanding of the pathogenesis of Type 2 diabetes.”
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