Natural compound helps reverse diabetes in mice

Researchers at Washington University School of Medicine in St. Louis have restored normal blood sugar metabolism in diabetic mice using a compound the body makes naturally. The finding suggests that it may one day be possible for people to take the compound much like a daily vitamin as a way to treat or even prevent type 2 diabetes.

This naturally occurring compound is called nicotinamide mononucleotide, or NMN, and it plays a vital role in how cells use energy.

"After giving NMN, goes completely back to normal in female diabetic mice," says Shin-ichiro Imai, MD, PhD, associate professor of . "In males, we see a milder effect compared to females, but we still see an effect. These are really remarkable results. NMN improves diabetic symptoms, at least in mice."

The research appears online Oct. 4 in .

This video is not supported by your browser at this time.
Researchers at Washington University School of Medicine in St. Louis have restored normal blood sugar metabolism in diabetic mice using a compound the body makes naturally. The finding suggests that it may one day be possible for people to take the compound much like a daily vitamin as a way to treat or even prevent type 2 diabetes. Credit: Jim Dryden

Imai says this discovery holds promise for people because the mechanisms that NMN influences are largely the same in mice and humans.

"But whether this mechanism is equally compromised in human patients with is something we have to check," Imai says. "We have plans to do this in the very near future."

All cells in the body make NMN in a chain of reactions leading to production of NAD, a vital molecule that energy from nutrients and puts it into a form cells can use. Among other things, NAD activates a protein called SIRT1 that has been shown to promote healthy metabolism throughout the body, from the to the liver to muscle and fat tissue.

According to the study, aging and eating a high-fat diet reduce production of NMN, slowing the body's production of NAD and leading to abnormal metabolic conditions such as diabetes. NAD cannot be given to the mice directly because of . But after administering NMN, levels of NAD rise and the diabetic mice show dramatically improved responses to glucose. In some cases, they return to normal.

"I'm very excited to see these results because the effect of NMN is much bigger than other known compounds or chemicals," says first author Jun Yoshino, MD, PhD, postdoctoral research associate. "Plus, the fact that the body naturally makes NMN is promising for translating these findings into humans."

Imai and his colleagues found that young, healthy mice on a high-fat diet developed diabetes in six months or less. In these mice, they found that NAD levels were reduced. But after administering NMN, levels of NAD increased and the female mice had normal results in glucose tolerance tests -- a measure of how well the body moves glucose from the blood to the organs and tissues for use. Glucose tolerance was also improved after male diabetic mice received NMN but did not quite return to normal. The researchers are interested in learning more about these differences between male and female mice.

"We don't have a clear answer, but we are speculating that sex hormones, such as estrogen, may be important downstream for NAD synthesis," Yoshino says.

In older mice, they observed that about 15 percent of healthy males fed a normal diet developed diabetes.

"When we injected these older diabetic mice with NMN, they had improved glucose tolerance, even after one injection," says Kathryn F. Mills, research lab supervisor and an equally contributing first author of the study. "We also injected older healthy mice and found that they weren't adversely affected. It's good to know that even if the mice are not diabetic, giving NMN is not going to hurt them."

Imai says few studies have examined normal mice that naturally develop diabetes as a simple result of aging because the experiments take so long. In an interesting twist, few elderly female mice developed diabetes at all. But after switching to a high fat diet, older female mice quickly developed severe diabetes.

"Again, when we injected these females with NMN, we came up with a completely normal glucose tolerance curve," Mills says. "We can also see that the NMN has completely reversed and normalized the levels of cholesterol, triglycerides and free fatty acids."

Though the received NMN by injection in this study, Imai's group is now conducting a long-term study of that get NMN dissolved in their drinking water. Imai calls this work a first step toward a possible "nutriceutical" that people could take almost like a vitamin to treat or even prevent type 2 diabetes.

"Once we can get a grade of NMN that humans can take, we would really like to launch a pilot human study," Imai says.

More information: Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metabolism. Online Oct. 4, 2011.

Related Stories

Fat cells send message that aids insulin secretion

Nov 06, 2007

The body's fat cells help the pancreas do its job of secreting insulin, according to research at Washington University School of Medicine in St. Louis. This previously unrecognized process ultimately could lead to new methods ...

Apelin hormone injections powerfully lower blood sugar

Nov 04, 2008

By injecting a hormone produced by fat and other tissues into mice, researchers report in the November Cell Metabolism that they significantly lowered blood sugar levels in normal and obese mice. The findings suggest that t ...

Recommended for you

Growing a blood vessel in a week

6 hours ago

The technology for creating new tissues from stem cells has taken a giant leap forward. Three tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This is shown ...

Testing time for stem cells

9 hours ago

DefiniGEN is one of the first commercial opportunities to arise from Cambridge's expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic ...

Team finds key signaling pathway in cause of preeclampsia

Oct 23, 2014

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

Oct 23, 2014

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments