U of T researchers one step closer to creating oral insulin

University of Toronto researchers have shown that “designer molecules” can interact with the body’s insulin receptor, a step toward the development of an oral medication for diabetes.

U of T professors Lakshmi Kotra, Cecil Yip, Peter Ottensmeyer and Robert Batey have created the first small molecules using the three-dimensional structure of the insulin receptor. A receptor is the site on the surface of a cell to which molecules with specific tasks, such as hormones, attach themselves. Insulin’s task is to initiate the utilization of sugar in the blood.

“This is the first time that a 3-D model of the insulin receptor on a cell surface has been created and used for drug design,” says Kotra, director of U of T’s Molecular Design and Information Technology Centre (MDIT). The study appears in the March 22 issue of Bioorganic & Medicinal Chemistry Letters.

The 3-D computer modelling of the receptor and the drug design were conducted at MDIT, a state-of-the-art computer modelling centre with resources for drug design. Researchers then used this knowledge to create specially-designed molecules that bind to the receptor in the same way insulin does. In so doing, they hope to develop a drug similar to insulin that can be taken orally. (Insulin itself must be injected directly into the bloodstream because it is broken down in the stomach if taken orally.)

More than two million Canadians have diabetes, and many of them require regular insulin injections to help their bodies absorb sugar properly. Research has shown self-injection to be a problem for children and the elderly, and lifelong regular injections are not pleasant for patients.

Previous efforts to create oral medications with insulin’s properties have failed, due to inadequate knowledge of the dynamics of the relationship between insulin and its receptor. Since the U of T team now understands this structural relationship, they can work to design novel molecules that mimic insulin’s therapeutic properties.

Other researchers included Ira Goldfine of the University of California, San Francisco, and U of T postdoctoral fellows Christopher Tan and Lianhu Wei. U of T Innovations Foundation is managing the commercialization of this discovery. This research is supported by Canadian Institutes of Health Research, Proof-of-Principle programs.

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Elaine Smith University of Toronto

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