Scientists Unlock How Insulin Interacts With Cells

Newswise The discovery of insulin nearly a century ago changed diabetes from a death sentence to a chronic disease.

Today a team that includes researchers from Case Western Reserve University School of Medicine announced a discovery that could lead to dramatic improvements in the lives of people managing diabetes.

After decades of speculation about exactly how insulin interacts with cells, the international group of scientists finally found a definitive answer: in an article published today in the journal Nature, the group describes how insulin binds to the cell to allow the cell to transform sugar into energyand also how the insulin itself changes shape as a result of this connection.

These findings carry profound implications for diabetes patients, said Case Western Reserve biochemistry professor and department chair Michael A. Weiss, MD, PhD, MBA, one of the leaders of the team. This new information increases exponentially the chances that we can develop better treatmentsin particular, oral medications instead of syringes, pens or pumps.

Weiss, also the Cowan-Blum Professor of Cancer Research at the School of Medicine, is renowned worldwide for his work on insulin. In 1991 he used nuclear magnetic resonance techniques to describe the structure of insulin; more recently he has developed a preliminary version of the hormone that does not need to be refrigerated, a critical breakthrough for those with diabetes in the developing world.

The results published today, however, represent among the most promising for Weiss and an entire generation of scientists devoted to enhancing care for those suffering from diabetes. They have sought to solve mystery of how the hormone bound to cells since 1969, when the late Dorothy Hodgkin and colleagues at the University of Oxford, first described insulins structure.

Theres been a logjam in our understanding since then, Weiss said. We hope that weve broken the logjam.

The magnitude of the challenge is, in part, evidenced by the diversity of the team required to overcome it. Weiss partnered with Associate Professor Mike Lawrence, of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, to lead the project. They, in turn, engaged scientists from the University of Chicago, the University of York in the United Kingdom, and the Institute of Organic Chemistry and Biochemistry in Prague in the Czech Republic.

The scientists recognized that cells absorb sugar from food as energy for the body, yet glucose cant penetrate a cells membrane without help from insulin, a hormone secreted from endocrine cells in the pancreas. To absorb the sugar, most cells have insulin receptors that bind the hormone as it flows through the bloodstream.

The researchers tested structural models using molecular-genetic methods to insert probes that, in turn, are activated by ultra-violet light into the receptor. The procedure creates highly detailed, three-dimensional imageswhich provided critical answers for Weiss, Lawrence and their colleagues.

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Scientists Unlock How Insulin Interacts With Cells

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