Nicotinamide Mononucleotide, a Key NAD(+) Intermediate, Treats the Pathophysiology of Diet- And Age-Induced Diabetes in Mice

Cell Metab. 2011 Oct 5;14(4):528-36. doi: 10.1016/j.cmet.2011.08.014.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Circadian Rhythm / genetics
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / 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

Substances

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