Editors' ChoiceDiabetes

A Supplement to Treat Diabetes?

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Science Translational Medicine  09 Nov 2011:
Vol. 3, Issue 108, pp. 108ec181
DOI: 10.1126/scitranslmed.3003369

Type 2 diabetes is an increasing health problem, and a well-known contributor to this epidemic is consumption of a high-fat diet. Now, Yoshino et al. demonstrate that administration of the naturally occurring molecule nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), promotes NAD+ biosynthesis and is effective in restoring normal blood glucose in mice with type 2 diabetes.

Adaptive metabolic pathways—an evolutionary response to nutritional deprivation—are down-regulated by a modern high-fat diet. One such metabolic pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the biosynthesis of NAD+. Among its numerous roles in energy metabolism, NAD+ activates a protein called Sirtuin 1 (SIRT1). Both NAMPT-mediated NAD+ biosynthesis and SIRT1 are known to regulate glucose-stimulated insulin secretion by pancreatic β cells.

In the Yoshino et al. study, healthy mice that were fed a high-fat diet developed overt diabetes within 6 months. The authors show that the concentration of NAD+ in the tissues of these mice was markedly reduced. Because NAD cannot be given to mice directly because of its toxicity, the mice were treated with subcutaneous injections of the NAD+ precursor, NMN, which boosted NAD+ concentrations and lowered blood glucose concentrations in the diabetic animals. Administration of NMN improved glucose tolerance in male diabetic mice and resulted in a normal glucose tolerance test in female diabetic mice. Moreover, NMN treatment also enhanced insulin sensitivity in liver tissue and reversed changes in gene expression related to oxidative stress and inflammation in liver as well as improving lipid homeostasis in the diabetic mice.

The underlying metabolic pathways influenced by NMN are similar in mice and humans. Thus, these findings may shed light on the relationship of NMN and NAD+ to obesity and type 2 diabetes in people. Although much more research is needed, it is intriguing to speculate whether NMN—a substance that occurs naturally in the human body—could be used as a treatment for type 2 diabetes.

J. Yoshino et al., Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14, 528536 (2011). [Full Text]

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