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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 RIS Download
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Consortium represents all publicly available gene trap cell lines, which are available on non-collaborative basis for nominal handling fees. Researchers can search and browse IGTC database for cell lines of interest using accession numbers or IDs, keywords, sequence data, tissue expression profiles and biological pathways, can find trapped genes of interest on IGTC website, and order cell lines for generation of mutant mice through blastocyst injection. Consortium members include: BayGenomics (USA), Centre for Modelling Human Disease (Toronto, Canada), Embryonic Stem Cell Database (University of Manitoba, Canada), Exchangeable Gene Trap Clones (Kumamoto University, Japan), German Gene Trap Consortium provider (Germany), Sanger Institute Gene Trap Resource (Cambridge, UK), Soriano Lab Gene Trap Resource (Mount Sinai School of Medicine, New York, USA), Texas Institute for Genomic Medicine - TIGM (USA), TIGEM-IRBM Gene Trap (Naples, Italy).
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