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Nampt/PBEF/Visfatin Regulates Insulin Secretion in β Cells as a Systemic NAD Biosynthetic Enzyme
Open accessAbstract
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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“Whereas NMN concentration has been reported to reach around 50 μM in plasma14, our study and others13 have failed to detect comparable levels of circulating NMN.”
From NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells (2016) · cites this paper as [14]
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“Since Nampt homozygous knockout mice (NAMPT-/-) have embryonic lethality 59”
From Nicotinamide phosphoribosyltransferase prompts bleomycin-induced pulmonary fibrosis by driving macrophage M2 polarization in mice (2024) · cites this paper as [59]
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Metadata
- 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
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 6
- Issue
- 5
- Pages
- 363-375
- ISSN
- 1550-4131 (ISSN-L)
- 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
- 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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