Cited by 912Sirtuins and Resveratrol in MedicinePancreatic function and diabetesAdipose Tissue and Metabolism

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

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Revollo, Javier R., Körner, Antje, Mills, Kathryn F., Satoh, Akiko, Wang, Tao, Garten, Antje, Dasgupta, Biplab, Sasaki, Yo, Wolberger, Cynthia, Townsend, R. Reid, Milbrandt, Jeffrey, Kiess, Wieland, Imai, Shin-ichiro·2007·Cell Metabolism

DOI 10.1016/j.cmet.2007.09.003PMC PMC2098698

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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.

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Self-citation

Authors: Revollo, J. R., Körner, A., Mills, K. F., Satoh, A., Wang, T., Garten, A., Dasgupta, B., Sasaki, Y., Wolberger, C., Townsend, R. R., Milbrandt, J., Kiess, W., & Imai, S.-I.
Affiliations: Washington University in St. Louis (US)
University Hospital Leipzig (DE)
Howard Hughes Medical Institute (US)
Corresponding author: Imai, Shin-ichiro
ORCID: Revollo, Javier R.
Körner, Antje
Satoh, Akiko
Wang, Tao
Garten, Antje
Dasgupta, Biplab
Wolberger, Cynthia
Milbrandt, Jeffrey
Kiess, Wieland
Imai, Shin-ichiro
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2007-11
Volume: 6
Issue: 5
Pages: 363-375
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2007.09.003
PMC: PMC2098698
OpenAlex: W2002811789
Cited by: 911
References: 41
Citations by year: 2026: 32 · 2025: 36 · 2024: 51 · 2023: 38 · 2022: 45 · 2021: 51 · 2020: 42 · 2019: 53 · 2018: 48 · 2017: 47 · 2016: 40 · 2015: 60 · 2014: 44 · 2013: 49 · 2012: 60
FWCI: 23.56
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2085 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Deutsche Forschungsgemeinschaft
Universität Ulm
National Institutes of Health (1c06rr015502-01)
National Institute on Aging (R01AG024150, AG024150)
National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK-52574, DK56341, P30DK056341, P30DK052574)
National Institute of Neurological Disorders and Stroke (NS36358)
National Center for Research Resources (C06-RR-015502, P41 RR00945)
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: visfatin, PBEF, NAD biosynthesis, insulin secretion, pancreatic beta cells, nicotinamide mononucleotide, glucose-stimulated insulin secretion, glucose homeostasis
MeSH terms: Animals, Adipose Tissue, Brown, Cell Differentiation, Cell Line, Female, Insulin, Islets of Langerhans, Kidney, Liver, Mice, Inbred C57BL, Myocardium, NAD, Nicotinamide Mononucleotide, Signal Transduction, Glucose Intolerance, Mice, Knockout, Immunoprecipitation, Insulin-Secreting Cells, Mice, Nicotinamide Phosphoribosyltransferase

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

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