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

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.

Pubmed ID: 17983582

Authors

  • Revollo JR
  • K├Ârner A
  • Mills KF
  • Satoh A
  • Wang T
  • Garten A
  • Dasgupta B
  • Sasaki Y
  • Wolberger C
  • Townsend RR
  • Milbrandt J
  • Kiess W
  • Imai S

Journal

Cell metabolism

Publication Data

November 6, 2007

Associated Grants

  • Agency: NIA NIH HHS, Id: AG024150
  • Agency: NCRR NIH HHS, Id: C06RR015502
  • Agency: NIDDK NIH HHS, Id: DK56341
  • Agency: NINDS NIH HHS, Id: NS36358
  • Agency: NIDDK NIH HHS, Id: P30 DK056341
  • Agency: NIDDK NIH HHS, Id: P30 DK056341-06
  • Agency: NIDDK NIH HHS, Id: P30 DK056341-07
  • Agency: NIDDK NIH HHS, Id: P30 DK52574
  • Agency: NCRR NIH HHS, Id: P41RR00945
  • Agency: NIA NIH HHS, Id: R01 AG024150
  • Agency: NIA NIH HHS, Id: R01 AG024150-04

Mesh Terms

  • Adipose Tissue, Brown
  • Animals
  • Cell Differentiation
  • Cell Line
  • Female
  • Glucose Intolerance
  • Immunoprecipitation
  • Insulin
  • Insulin-Secreting Cells
  • Islets of Langerhans
  • Kidney
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardium
  • NAD
  • Nicotinamide Mononucleotide
  • Nicotinamide Phosphoribosyltransferase
  • Signal Transduction