Complete structure of Insulin receptor discovered - may assist in drug development for diabetes

By Dr. Ananya Mandal, MDMar 24 2010

Insulin is one of the most commonly used therapeutic agents used in diabetes. While the structure of this complex protein has been studied in detail there were parts of the receptor for insulin that were not clearly defined till now. This receptor is a protein that exists on the surfaces of cells and binds to the insulin molecule. These receptors are responsible for the action of insulin on the cells.

Now Walter and Eliza Hall Institute researchers have uncovered the whole molecular structure of this receptor molecule. Armed with this knowledge, development of new therapies might be possible for diabetes.

Australian scientists in 2006 has discovered a large portion of this receptor molecule, but the key portion where the insulin molecule binds was still not found. They had initially used protein crystallography to image the insulin receptor protein and had discovered two elements that made up the receptor. The first element was clear but it is only now that the second element is revealed.

Now, Drs Mike Lawrence, Brian Smith, John Menting, Geoffrey Kong and Colin Ward from the institute’s Structural Biology division, together with colleagues from the Case Western Reserve University and the University of Chicago, have worked out the molecular structure of this key segment.

These findings have been reported in the Proceedings of the National Academy of Sciences USA early edition.

Dr Lawrence said “You can’t work it out unless you have a view of the site to which the insulin binds, and that’s what we’ve done,” he said. “By understanding how insulin binds and transmits messages into the cell we will be in a better position to design compounds that mimic insulin and could be used to treat diabetes.”

This team is also involved in another important aspect involving the structure of related Type 1 insulin-like growth factor receptor, to which insulin-like growth factors bind.

“These structures are not currently known, despite their considerable importance and direct relevance to the design of new drugs for cancer, Alzheimer’s disease and diabetes - three of the most critical diseases facing Australia,” Dr Lawrence said.

“By understanding how insulin binds and transmits messages into the cell we will be in a better position to design compounds that mimic insulin and could be used to treat diabetes,” said Dr Lawrence.

According to Dr. Lawrence these findings can also lead to new avenues in the development of insulin that can be taken by mouth instead of daily painful injections. Apart from this, newer formulations of faster acting and longer lasting insulin can also be developed from this knowledge.