DXM can boost insulin in type 2 diabetics

[Green Fox]

http://arstechnica.com/science/2015/...boost-insulin/

Scientific Method / Science & Exploration
A common over-the-counter cough suppressant can boost insulin
Type 2 diabetics could benefit from a drug that's already on the market.

by Diana Gitig - Mar 18, 2015 11:16am CDT

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In this image, the insulin-producing cells glow green.
NIH

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 medicines that make life so much more bearable when you're coughing your lungs out. It's not good for everyone though; the American Academy of Pediatricians has recommended that it not be given to children under the age of four, because it is completely ineffective for them and may even cause them harm.

But although it may be bad for kids, it may be good for type 2 diabetics; a recent report in Nature Medicine 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's called the 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 the patients who take these drugs. New types of drugs that only boost insulin in response to glucose are thus highly desirable.

To do that, we need to be able to manipulate the pancreas. It's a somewhat unusual organ; many neural receptors are also found in pancreatic islet cells and, as of now, we don't really know what we are doing there. So some researchers in Europe decided they might be the key to tweaking the pancreas' activity.

In the brain, NMDA receptors are the ones targeted by DXM. To see what NMDA receptors are doing in pancreatic islet cells, these researchers took the tried and true approach of eliminating them and seeing what happened. The researchers removed the receptors genetically by knocking them out in mice. They also removed them pharmacologically, by treating mice with DXM and other molecules that block signaling through these receptors.

When the NMDA receptors were removed, either genetically or functionally, glucose-stimulated insulin secretion went up. Importantly, basal insulin secretion did not. DXM targets other receptors and neural tissues, so it could be acting indirectly, via the nervous system. To confirm that DXM enhanced glucose-stimulated insulin secretion by blocking the NMDA receptors in the islet cells, the researchers checked if DXM could achieve the same effect in islet cells from the NMDA knockout mice. It could not, confirming that it must in fact act through these receptors.

Results in mouse cells, human cells, and mouse models of type 2 diabetes were so promising that the researchers were able to perform a registered phase 2a double-blinded, placebo-controlled, randomized study on twenty men with type 2 diabetes. The real deal. Participants were all already taking metformin, an antidiabetes drug that inhibits the synthesis of glucose in the liver. 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 eliciting hypoglycemia. Remember, this is an over the counter cough suppressant we're talking about here.

In addition to suggesting a potential new drug for diabetes, this work has made a great start at determining what NMDA receptors are doing in pancreatic islet cells; they help regulate insulin release and thus contribute to controlling blood sugar.

[Ankh]

great!
maybe now, they'll take out the insane amount of high fructose corn syrup and i can swig in peace ;)

[viscosity]

Really interesting, thanks for finding that.

I know this study was done in mice, but it's nice to think that perhaps DXM has somewhat protected my body from all those years of drinking Wyeth's high fructose syrup laden DXM concoctions (aka Robitussin).

[libel]

I always thought this was interesting. I wouldn't recommend extended dosing that would allow for up-regulation, however.

http://www.ncbi.nlm.nih.gov/pubmed/22763259

DXO is more relevant at the sigma-2 receptor than DXO, IIRC.

So this reminds me of some prior research concerning apoptosis via sigma-2 agonism.


Also, this was from some older research that I refer to, to exercise caution.

http://www.dextroverse.org/forums/en...got-the-beetus