Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme

Cell Metab. 2007 Nov;6(5):363-75. doi: 10.1016/j.cmet.2007.09.003.

Abstract

Intracellular nicotinamide phosphoribosyltransferase (iNampt) is an essential enzyme in the NAD biosynthetic pathway. An extracellular form of this protein (eNampt) has been reported to act as a cytokine named PBEF or an insulin-mimetic hormone named visfatin, but its physiological relevance remains controversial. Here we show that eNampt does not exert insulin-mimetic effects in vitro or in vivo but rather exhibits robust NAD biosynthetic activity. Haplodeficiency and chemical inhibition of Nampt cause defects in NAD biosynthesis and glucose-stimulated insulin secretion in pancreatic islets in vivo and in vitro. These defects are corrected by administration of nicotinamide mononucleotide (NMN), a product of the Nampt reaction. A high concentration of NMN is present in mouse plasma, and plasma eNampt and NMN levels are reduced in Nampt heterozygous females. Our results demonstrate that Nampt-mediated systemic NAD biosynthesis is critical for beta cell function, suggesting a vital framework for the regulation of glucose homeostasis.

Publication types

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

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Animals
  • Cell Differentiation
  • Cell Line
  • Female
  • Glucose Intolerance
  • Immunoprecipitation
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Kidney / metabolism
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardium / metabolism
  • NAD / biosynthesis*
  • Nicotinamide Mononucleotide / blood
  • Nicotinamide Mononucleotide / metabolism
  • Nicotinamide Mononucleotide / pharmacology
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Nicotinamide Phosphoribosyltransferase / metabolism*
  • Signal Transduction / drug effects

Substances

  • Insulin
  • NAD
  • Nicotinamide Mononucleotide
  • Nicotinamide Phosphoribosyltransferase