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Biological Chemistry

Cough Suppressant Tames Type 2 Diabetes

Medicinal Chemistry: Ingredient in over-the-counter medicine blocks receptor on insulin-producing pancreatic cells

by Elizabeth K. Wilson
March 19, 2015 | A version of this story appeared in Volume 93, Issue 12

Laser scanning microscopy images of human islet cells.
Credit: Alena Welters, Institute of Metabolic Physiology, Heinrich-Heine-U Düsseldorf/Nature Medicine
When treated only with cytokines (left), islet cells from a human with type 2 diabetes die (red). When additionally treated with a metabolite of dextromethorphan (right), more islet cells survive.

A new study suggests that the over-the-counter cough suppressant dextromethorphan and compounds like it could boost the effectiveness of current treatments for type 2 diabetes (Nat. Med. 2015, DOI:10.1038/nm.3822).

These molecules block glutamate receptors—otherwise known as NMDA receptors—typically found on nerve cells, where they’re involved in numerous functions, including nervous system development and cognition. The receptors also exist in pancreatic cell clusters known as islets. But NMDA receptors’ function there has remained mysterious.

Type 2 diabetes, a condition characterized by glucose intolerance and inadequate insulin production, affects millions of adults. Various drugs can treat the disease, but they can cause hypoglycemia and other problems, and they don’t halt progressive damage of islet cells.

Now, an international team led by Eckhard Lammert, a professor at Heinrich Heine University and the German Diabetes Center, both in Düsseldorf, Germany, has discovered a significant link between NMDA receptors and islet cell function.

The group exposed cultures of islet cells from both mice and humans with type 2 diabetes to small signaling proteins called cytokines, causing islet cell damage and death. But when the islets were also treated with a metabolite of dextromethorphan—also an NMDA receptor blocker—many more islet cells survived.

Lammert’s team also found that long-term treatment with dextromethorphan helped control blood glucose concentrations in mice engineered to develop type 2 diabetes.

Finally, the group conducted a human clinical trial of 20 patients. Those who took dextromethorphan showed improved glucose tolerance and enhanced glucose-stimulated blood insulin concentrations.

Patrik Rorsman, a professor at Oxford Centre for Diabetes, Endocrinology & Metabolism, calls the work “newsworthy and noteworthy” and says the NMDA receptor-diabetes connection is “an interesting and unexpected mechanism.”



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