Nicotinamide Mononucleotide Restores Glucose Balance in Diabetic Mouse Model

The naturally occurring compound nicotinamide mononucleotide (NMN) was found to restore correct glucose metabolism in a mouse model of high fat diet (HFD) and age-induced type II diabetes.

One metabolic pathway that malfunctions in type II diabetes is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis, and the NAD+-dependent protein deacetylase SIRT1. SIRT1 has been linked to healthy metabolism throughout the body, including organs like the pancreas and liver, which are directly linked to type II diabetes.

In the current study researchers at the Washington University School of Medicine (St. Louis, MO, USA) worked with both young, healthy mice that were fed a high fat diet and a group of older animals that were fed either regular or high fat diets.

They reported in the October 5, 2011, online edition of the journal Cell Metabolism that independent of the cause of the diabetes (high fat diet or old age), injections of nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD+ intermediate, corrected the animals' glucose intolerance by restoring NAD+ levels. NMN also enhanced the liver's insulin sensitivity and restored gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Treatment with NMN had no apparent side effects on either diabetic or normal mice.

In addition to its ability to normalize glucose tolerance NMN completely reversed and normalized the levels of cholesterol, triglycerides, and free fatty acids in many of the diabetic mice.

"After giving NMN, glucose tolerance goes completely back to normal in female diabetic mice," said senior author Dr. Shin-ichiro Imai, associate professor of developmental biology at the Washington University School of Medicine. "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. Once we can get a grade of NMN that humans can take, we would really like to launch a pilot human study."

Related Links:
Washington University School of Medicine