In this image, the insulin-producing cells glow green.
Dextromethorphan (DXM) is a cough suppressant found in Vick’s NyQuil Cold & Flu Relief, Triaminic Multi-Symptom Fever, Dimetapp Children’s Multi-Symptom Cold & Flu, Tylenol Cold Multi-Symptom Nighttime, and similar over-the-counter cold remedies that make life so much more bearable when you cough your lungs out. However, it is not good for everyone; the American Academy of Pediatricians has recommended that it should not be given to children under the age of four, as it is completely ineffective for them and may even be harmful.
But while it may be bad for kids, it can be good for type 2 diabetics; a recent report Naturopathy suggests that it increases glucose tolerance and does so in a way that is more effective than existing drugs.
Antidiabetic drugs currently on the market increase what are called basal levels of insulin secretion – it goes up all the time, whether it’s needed or not. This basal insulin secretion is a major cause of lethal hypoglycemia in patients taking these medications. Thus, new types of drugs that stimulate insulin only in response to glucose are highly desirable.
To do that, we need to be able to manipulate the pancreas. It is a somewhat unusual organ; many neural receptors are also found in cells of pancreatic islets and as of now we don’t really know what we’re doing there. So some researchers in Europe decided they could hold the key to modifying pancreatic activity.
In the brain, NMDA receptors are targeted by DXM. To see what NMDA receptors do in pancreatic islet cells, these researchers took the tried and true approach of knocking them out and seeing what happened. The researchers genetically removed the receptors by switching them off in mice. They also removed them pharmacologically by treating mice with DXM and other molecules that block signal transmission through these receptors.
When the NMDA receptors were deleted genetically or functionally, glucose-stimulated insulin secretion increased. Importantly, basal insulin secretion did not. DXM targets other receptors and neural tissues, so it may act indirectly, via the nervous system. To confirm that DXM improved glucose-stimulated insulin secretion by blocking the NMDA receptors in the islet cells, the researchers checked whether DXM could achieve the same effect in islet cells from the NMDA knockout mice. It couldn’t, confirming that it must in fact work through these receptors.
The results in mouse cells, human cells and mouse models of type 2 diabetes were so promising that the researchers were able to conduct a registered double-blind, placebo-controlled, randomized phase 2 study in twenty men with type 2 diabetes. The real thing. The participants were all already taking metformin, an antidiabetic drug that inhibits the synthesis of glucose in the liver. The results were consistent with those seen in tissue culture and animal studies: DXM increased islet cell viability, glucose-stimulated insulin secretion and glucose tolerance – all without inducing hypoglycemia. Remember this is an over the counter cough suppressant we are talking about here.
In addition to suggesting a potential new drug for diabetes, this work is off to a good start in determining what NMDA receptors do in pancreatic islet cells; they help regulate insulin release and thus contribute to blood sugar control.
Naturopathy2014. DOI: 10.1038/nm.3822 (About DOIs).
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