Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice.

Abstract

Type 2 diabetes (T2D) has become epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD(+) biosynthesis, and the NAD(+)-dependent protein deacetylase SIRT1. Here, we show that NAMPT-mediated NAD(+) biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD(+) intermediate, ameliorates glucose intolerance by restoring NAD(+) levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD(+) and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a potential nutriceutical intervention against diet- and age-induced T2D.

• Authors: Jun Yoshino, Kathryn F Mills, Myeong Jin Yoon, Shin-ichiro Imai
• Journal: Cell metabolism (Cell Metab) Vol. 14 Issue 4 Pg. 528-36 (Oct 05 2011) ISSN: 1932-7420 [Electronic] United States
• PMID: 21982712 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Hypoglycemic Agents
• Insulin
• NAD
• Nicotinamide Mononucleotide
• Nicotinamide Phosphoribosyltransferase
• nicotinamide phosphoribosyltransferase, mouse
• Sirt1 protein, mouse
• Sirtuin 1
• Glucose

Topics

• Aging
• Animals
• Circadian Rhythm (genetics)
• Cytokines (metabolism)
• Diabetes Mellitus, Type 2 (metabolism, physiopathology)
• Diet, High-Fat
• Disease Models, Animal
• Gene Expression Regulation
• Glucose (metabolism)
• Hypoglycemic Agents (pharmacology)
• Insulin (metabolism)
• Lipid Metabolism
• Mice
• NAD (biosynthesis)
• Nicotinamide Mononucleotide (pharmacology)
• Nicotinamide Phosphoribosyltransferase (metabolism)
• Oxidative Stress (genetics)
• Sirtuin 1 (metabolism)