Nampt/PBEF/Visfatin Regulates Insulin Secretion in β Cells as a Systemic NAD Biosynthetic Enzyme

Javier R. Revollo, Antje Körner, Kathryn F. Mills, Akiko Satoh, Tao Wang, Antje Garten, Biplab Dasgupta, Yo Sasaki, Cynthia Wolberger, R. Reid Townsend, Jeffrey Milbrandt, Wieland Kiess, Shin ichiro Imai

Research output: Contribution to journalArticle

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 β cell function, suggesting a vital framework for the regulation of glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)363-375
Number of pages13
JournalCell Metabolism
Volume6
Issue number5
DOIs
StatePublished - Nov 7 2007

Keywords

  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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