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Slc12a8 is a nicotinamide mononucleotide transporter
Open accessAbstract
Nicotinamide mononucleotide (NMN) is a biosynthetic precursor of NAD+ known to promote cellular NAD+ production and counteract age-associated pathologies associated with a decline in tissue NAD+ levels. How NMN is taken up into cells has not been entirely clear. Here we show that the Slc12a8 gene encodes a specific NMN transporter. We find that Slc12a8 is highly expressed and regulated by NAD+ in the murine small intestine. Slc12a8 knockdown abrogates the uptake of NMN in vitro and in vivo. We further show that Slc12a8 specifically transports NMN, but not nicotinamide riboside, and that NMN transport depends on the presence of sodium ion. Slc12a8 deficiency significantly decreases NAD+ levels in the jejunum and ileum, which is associated with reduced NMN uptake as traced by doubly labeled isotopic NMN. Finally, we observe that Slc12a8 expression is upregulated in the aged murine ileum, which contributes to the maintenance of ileal NAD+ levels. Our work identifies the first NMN transporter and demonstrates that Slc12a8 has a critical role in regulating intestinal NAD+ metabolism.
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“The expression of a transporter in the gut [76] reinforces that NMN could be made bioavailable through oral delivery.”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [76]
In the citing paper
“A newly reported NMN transporter, the Slc12a8, is highly expressed and regulated by NAD+, in the murine small intestine, and Slc12a8 deficiency abrogates the uptake of NMN in vitro and in vivo (Grozio et al., 2019).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Grozio et al., 2019
In the citing paper
“through a transporter called slc12a8, 26-month-old mice (equivalent to 70 human years) that took NMN increased their NAD+ levels to close to 3 months old (equivalent to 12 human months). The content level in young mice increased the cell energy in aged mice [208].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [208]
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Cites
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“NMN is transported by SLC12A8 (Grozio et al., 2019) with QD conjugation facilitating a 10fold increase in its transportation by pinocytosis and clathrinmediated endocytosis in vitro (Hunt et al.”
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“A transport protein called SLC12A8, which was highly expressed on the membrane of the small intestine mucosa, was involved in the transportation of NMN (a direct substrate for the synthesis of NAD) out of cells, with the assistance of sodium ions [51].”
BackgroundNAD metabolism in aging and cancer
Kincaid, J. W. R., & Berger, N. A. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220929287 · Cited by 29
“The work of Grozio et al.(66) identified the first NMN transporter, which is encoded by the Slc12a8 gene and requires the presence of sodium ions for activity.”
MethodGruenbacher, G., Gander, H., Rahm, A., Dobler, G., Drasche, A., Troppmair, J., Nußbaumer, W., & Thurnher, M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01870 · Cited by 27
“Intriguingly, NAD as well as its immediate precursor NMN, which are both known to permeate the plasma membrane and replenish intracellular pools during FK-866 induced depletion (37, 38), could restore P2Y11 receptor upregulation during NAMPT inhibition.”
BackgroundHypothalamic NAD+-Sirtuin Axis: Function and Regulation
Roh, E., & Kim, M. (2020) · Biomolecules · doi:10.3390/biom10030396 · Cited by 30
“It has recently been reported that the Slc12a8 gene encodes a specific NMN transporter expressed in the mouse small intestine [143].”
BackgroundWu, W., Yuan, S., Tang, Y., Meng, X., Peng, M., Hu, Z., & Liu, W. (2023) · Nutrients · doi:10.3390/nu15132851 · Cited by 33
“The highest expression of SLC12A8, the transporter protein of NMN, has been found in the small intestine, so the most significant increase in NAD+ has been detected in the small intestine after NMN administration [19,36].”
BackgroundMethodInfluentialChanneling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and Death
Reddy, V. G., Krider, I. S., Alves, E. T. M., Courey, J. M., Laham, M. S., & Thatcher, G. R. J. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c02112 · Cited by 27
Advancements in NMN biotherapy and research updates in the field of digestive system diseases
Liao, G., Xie, Y., Peng, H., Li, T., Zou, X., Yue, F., Guo, J., & Rong, L. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05614-9 · Cited by 27
“Moreover, NMN’s ability to activate sirtuins and regulate cellular senescence pathways suggested a multifaceted approach in cancer treatment [9, 77].”
BackgroundInfluentialThe Science Behind NMN-A Stable, Reliable NAD+Activator and Anti-Aging Molecule.
Shade, C. W. (2020) · Europe PMC (PubMed Central) · Cited by 24
NAD+ Metabolism and Interventions in Premature Renal Aging and Chronic Kidney Disease
Chanvillard, L., Tammaro, A., & Sorrentino, V. (2022) · Cells · doi:10.3390/cells12010021 · Cited by 28
“Indeed, it seems that NMN requires to be dephosphorylated by CD73 before entering the cells as NR where it can be phosphorylated back to NMN [49], even though a specific NMN transporter highly expressed in the small intestine has been recently discovered [50].”
BackgroundRecent Neurotherapeutic Strategies to Promote Healthy Brain Aging: Are we there yet?
Kim, C.-K., Sachdev, P. S., & Braidy, N. (2022) · Aging and Disease · doi:10.14336/ad.2021.0705 · Cited by 27
“Recently, a genetic, pharmacological and kinetic study reported that NMN is dephosphorylated to NR before cellular internalization by the solute carrier family 12 member 8 (Slc12a8) [175].”
BackgroundNitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions
Peters, J. P., Brahms, A., Janicaud, V., Anikeeva, M., Peschke, E., Ellermann, F., Ferrari, A., Hellmold, D., Held‐Feindt, J., Kim, N.-M., et al. (2023) · Science Advances · doi:10.1126/sciadv.add3643 · Cited by 25
“Recent findings suggest that NMN uptake is possible through SLC12A8 transporters (76) or via equilibrated nucleoside transporters following cleavage of NMN to NR by CD73 (77).”
Interacting NAD + and Cell Senescence Pathways Complicate Antiaging Therapies
Mendelsohn, A. R., & Larrick, J. W. (2019) · Rejuvenation Research · doi:10.1089/rej.2019.2218 · Cited by 25
“…NMN has to be converted to uncharged NR by CD73 to enter cells, but the recent identification of Slc12a8 as an NMN transporter in the gut of mice 25 and widely expressed in many tissues (Human Protein Atlas) suggests that oral NMN could be directly absorbed by the gut and subsequently most…”
Wang, Y., Yang, J.-S., Zhao, M., Chen, J., Xie, H.-X., Yu, H., Liu, N.-H., Yi, Z.-J., Liang, H., Xing, L., et al. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115355 · Cited by 26
NAD+ metabolism and therapeutic strategies in cardiovascular diseases
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Benjamin, C., & Crews, R. (2024) · Metabolites · doi:10.3390/metabo14060341 · Cited by 25
“Grozio et al. provided evidence supporting the chosen analytical technique in a subsequent publication [21,45].”
BackgroundSLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters
Chen, M., Yuan, L., Chen, B., Chang, H., Luo, J., Zhang, H., Chen, Z., Kong, J., Yi, Y., Bai, M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56402-y · Cited by 30
Innate immunity dysregulation in aging eye and therapeutic interventions
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“Two recent studies have proposed a role for sodium-dependent channels SLC6A17 and SLC12A8 in the import of NAD+ and NMN respectively 60,61 .”
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Franczyk, M. P., Qi, N., Stromsdorfer, K. L., Li, C., Yamaguchi, S., Itoh, H., Yoshino, M., Sasaki, Y., Brookheart, R. T., Finck, B. N., et al. (2021) · Endocrinology · doi:10.1210/endocr/bqab006 · Cited by 23
Self-citationDuan, H., Yu, Q., Ni, Y., Li, J., Yu, L., Yan, X., & Fan, L. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.135098 · Cited by 24
Nicotinamide Mononucleotide: Research Process in Cardiovascular Diseases
Deng, H., Ding, D., Ma, Y., Zhang, H., Wang, N., Zhang, C., & Yang, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179526 · Cited by 25
“The Slc12a8 gene is highly expressed in the pancreas and small intestine and moderately expressed in the white adipose tissue and liver, and it encodes a cell membrane-specific transporter that directly mediates NMN transportation through a sodium-dependent mechanism [20].”
BackgroundTransporters in vitamin uptake and cellular metabolism: impacts on health and disease
Yuan, Y., & Chen, L. (2025) · Life Metabolism · doi:10.1093/lifemeta/loaf008 · Cited by 25
The hidden side of the human FAD synthase 2
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The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies
Zhang, S., Azlan, N. F. M., Josiah, S. S., Zhou, J., Xiaoxia, Z., Jie, L., Zhang, Y., Dai, C., Liang, D., Li, P., et al. (2023) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2023.09.002 · Cited by 29
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Obrador, E., Palmer, R. S., López‐Blanch, R., Dellinger, R. W., & Estrela, J. M. (2021) · Biomedicines · doi:10.3390/biomedicines9081000 · Cited by 23
“Nevertheless, in rodents, it has been found that orally administered NMN quickly enters the cells of the small intestine through the Slc12a8 NMN transporter, and then is used to generate NAD+ [60].”
MethodDhuguru, J., Dellinger, R. W., & Migaud, M. E. (2023) · Nutrients · doi:10.3390/nu15133064 · Cited by 23
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“NR is a critical candidate for drug development as NMN can only be transported into cells by Slc12a8, while the dephosphorylated form of NR can be readily transported [143].”
BackgroundKitada, M., Araki, S., & Koya, D. (2023) · Cells · doi:10.3390/cells12040595 · Cited by 21
“NMN itself can be taken up via Slc12a8 [45].”
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“11 – – Radiologic involvement 64 (42) – – DAS28, mean ± SD 3.”
Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects
Yamane, T., Imai, M., Bamba, T., & Uchiyama, S. (2023) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2023.04.031 · Cited by 20
Nicotinamide Adenine Dinucleotide Deficiency and Its Impact on Mammalian Development
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“SLC12A8, first classified as a cation/chloride cotransp-orter, has been identified as a specific transporter for NMN (Grozio et al., 2019).”
Scalable syntheses of traceable ribosylated NAD + precursors
Makarov, M. V., Harris, N. W., Rodrigues, M. D. S., & Migaud, M. E. (2019) · Organic & Biomolecular Chemistry · doi:10.1039/c9ob01981b · Cited by 20
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“However, the expression of NMN transporter Slc12a8 (Grozio et al., 2019) and nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD+ salvage pathway (Burgos, 2011), was similar in two genotypes (Figure 7J).”
BackgroundNagahisa, T., Yamaguchi, S., Kosugi, S., Homma, K., Miyashita, K., Irie, J., Yoshino, J., & Itoh, H. (2022) · Endocrinology · doi:10.1210/endocr/bqac023 · Cited by 19
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“The discovery of the elusive NMN transporter, Slc12a8, in 2019, during a furious debate on whether NMN is cell permeable, is noteworthy [41].”
BackgroundSafety Evaluation for Restorin® NMN, a NAD+ Precursor
Turner, J. R., Licollari, A., Mihalcea, E., & Tan, A. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.749727 · Cited by 19
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“However, NMN could be transported into cells through Slc12a8, whereas Slc12a8 knockdown abrogated the uptake of NMN in vitro and in vivo [28].”
BackgroundTriple-Isotope Tracing for Pathway Discernment of NMN-Induced NAD+ Biosynthesis in Whole Mice
Sauve, A. A., Wang, Q., Zhang, N., Kang, S., Rathmann, A., & Yang, Y. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241311114 · Cited by 19
“Nevertheless, we observed a neglectable amount of NMN uptake, indicated by less than 1% m/z = 669 intensities, in the intestine after either administration route (Figure 6), which is not in agreement with the high expression of the putative NMN transporter Slc12a8 in the jejunum and ileum [20].”
BackgroundResultLactobacillus gasseri PA-3 directly incorporates purine mononucleotides and utilizes them for growth
Yamada, N., Saito, C., Kano, H., Fukuuchi, T., Yamaoka, N., Kaneko, K., & Asami, Y. (2020) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257770.2020.1815768 · Cited by 18
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“A recent study demonstrated that SLC12A8 is a nicotinamide mononucleotide transporter [17].”
BackgroundSIRT1-dependent restoration of NAD+ homeostasis after increased extracellular NAD+ exposure
Buonvicino, D., Ranieri, G., Pittelli, M. G., Lapucci, A., Bragliola, S., & Chiarugi, A. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100855 · Cited by 17
“Additional contributions, however, show that extracellular NAD+ (eNAD+) can be degraded by the ecto-50-nucleotidase (CD73) into NMN and NR (38, 39), with the former being hydrolyzed by CD38 into nicotinamide (NAM) and ribose 5phosphate (40) or transported intracellularly by the solute carrier family 12 member 8 (Slc12…”
BackgroundChini, C. C. S., Peclat, T., Gomez, L. S., Zeidler, J. D., Warner, G. M., Kashyap, S., Mazdeh, D. Z., Hayat, F., Migaud, M. E., Paulus, A., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.840246 · Cited by 17
“In contrast, gene expression of CD73 and the putative NMN transporter SLC12A8 (30) were increased, while other enzymes and transporters did not significantly change (Figure 4C).”
BackgroundSelf-citationDuan, H., Yu, Q., Ni, Y., Li, J., Yu, L., Yan, X., & Fan, L. (2024) · Food Bioscience · doi:10.1016/j.fbio.2024.104615 · Cited by 18
Reply to: Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter
Grozio, A., Mills, K. F., Yoshino, J., Bruzzone, S., Sociali, G., Tokizane, K., Lei, H. C., Sasaki, Y., Migaud, M. E., & Imai, S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0086-z · Cited by 16
Self-citationLong-term NMN treatment increases lifespan and healthspan in mice in a sex dependent mannerPreprint
Kane, A. E., Chellappa, K., Schultz, M. B., Arnold, M. W., Li, J., Amorim, J., Diener, C., Zhu, D., Mitchell, S. J., Griffin, P. T., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.21.599604 · Cited by 16
NAD+ metabolism in peripheral neuropathic pain
Dai, Y., Lin, J., Ren, J., Zhu, B., Wu, C., & Yu, L. (2022) · Neurochemistry International · doi:10.1016/j.neuint.2022.105435 · Cited by 15
Nagahisa, T., Kosugi, S., & Yamaguchi, S. (2023) · Nutrients · doi:10.3390/nu15061494 · Cited by 14
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“In the small intestine, SLC12A8, an NMN transporter, is highly expressed, which suggests that NMN may be an entry point into the nucleoside NAD+ synthesis pathway [203].”
BackgroundRen, C., Shuang, Z., Chen, Y., Deng, K., Kuang, M., Gong, Z., Zhang, K., Wang, P., Huang, P., Zhou, Z., et al. (2024) · The FASEB Journal · doi:10.1096/fj.202400453r · Cited by 14
“153 Intravenous injection of 50 mg/kg NMN is barely detectable in the bloodstream but results in increased circulating NR. 39,40 Conversely, after oral administration of isotopically labeled high-dose NR (200 mg/kg), labeled NAD + appears in the liver but is not detected in muscle or kidneys.”
InfluentialHashimoto, S., Gamage, U. S. K., Inoue, Y., Iwata, H., & Morimoto, Y. (2025) · Scientific Reports · doi:10.1038/s41598-024-81393-z · Cited by 15
Palmer, R. D., Elnashar, M. M. M., & Vaccarezza, M. (2021) · Aging Medicine · doi:10.1002/agm2.12170 · Cited by 13
“Ultimately, Schmidt and Brenner40 point out that levels of NAD are 500 times higher than NMN in normal liver samples, and Grozio et al. (2019) had failed to examine background/control levels, which undermines any result Grozio et al. (2019) delivered.”
BackgroundInfluentialUnno, J., Mills, K. F., Ogura, T., Nishimura, M., & Imai, S. (2024) · npj Aging · doi:10.1038/s41514-023-00133-1 · Cited by 13
“However, whereas the observed time courses and changes in plasma NMN levels in young and old mice were highly consistent with our previous results 14,24 , the absolute values of plasma NMN levels measured by the dimeLC-MS/MS methodology were much lower than those measured by the HPLC-based…”
InfluentialSelf-citationCross-talk in NAD+ metabolism: insights from Saccharomyces cerevisiae
Raj, C. J. T., & Lin, S.-J. (2019) · Current Genetics · doi:10.1007/s00294-019-00972-0 · Cited by 13
Damschroder, D., Perez, R. Z., Richardson, K., Vaz, F. M., Houtkooper, R. H., & Wessells, R. J. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049279 · Cited by 13
“…with NR transported directly into the cell, and NMN either converted to NR by CD73 and then transported into the cell (Garavaglia et al., 2012; Grozio et al., 2013; Ratajczak et al., 2016; Rajman et al., 2018) or directly transported by SLC12A8 in the small intestine (Grozio et al., 2019).”
Feuz, M. B., Meyer‐Ficca, M. L., & Meyer, R. G. (2023) · Cells · doi:10.3390/cells12030500 · Cited by 18
SLC12A8 plays a key role in bladder cancer progression and EMT
Li, S., Li, Z.-F., Cao, Q., & Wang, W.-Z. (2020) · Open Medicine · doi:10.1515/med-2021-0013 · Cited by 13
Risks and rewards of targeting NAD+ homeostasis in the brain
Li, C., & Wu, L. E. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111545 · Cited by 14
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Colonic mechanism of serum NAD+ depletion induced by DEHP during pregnancy
Hong, Y. S., Ning, X., Liang, Y.-Y., Li, X., Cui, Y., Wu, W., Cai, Y., Zhao, S., Zhu, M., Zhong, T.-X., et al. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.162188 · Cited by 12
U-Din, M., de Mello, V. D., Tuomainen, M. H., Raiko, J. R. H., Niemi, T. S., Fromme, T., Klåvus, A., Gautier, N., Haimilahti, K., Lehtonen, M., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113131 · Cited by 17
The elusive NMN transporter is found
Wu, L. E., & Sinclair, D. A. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0015-6 · Cited by 12
Nicotinamide mononucleotide: An emerging nutraceutical against cardiac aging?
Wei, Z., Chai, H., Chen, Y., Cheng, Y., & Liu, X. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.08.006 · Cited by 13
Wang, E., Wang, Y., Zhang, Z., Jiang, Y., & Zhao, C. (2025) · Biogerontology · doi:10.1007/s10522-025-10270-7 · Cited by 11
“This gene, highly expressed in the pancreas and small intestine, encodes a cell membrane-specific transporter that directly mediates NMN transmembrane transport through a sodium-dependent mechanism (Grozio et al. 2019).”
The Wnt–NAD+ axis in cancer, aging, and tissue regeneration
Lamprecht, J., Sanad, S. M., Kusumbe, A. P., & Habib, S. J. (2025) · Trends in Cell Biology · doi:10.1016/j.tcb.2025.07.006 · Cited by 14
Kang, S., Park, J.-W., Cho, E., Kim, D., Ye, S., Jeong, E. T., Jun, S., & Kang, N. G. (2025) · Biomedicines · doi:10.3390/biomedicines13102395 · Cited by 13
“…NMN has been considered one of the most effective precursors for administration due to the following reasons: (1) higher stability, both biologically and chemically [22,23], (2) smaller molecular size than that of NAD + , and (3) easier penetration into cells than NAD + through Slc12a8 [24].”
InfluentialLiver transcriptome profiles of dairy cows with different serum metabotypes
Ghaffari, M. H., Sadri, H., Trakooljul, N., Koch, C., & Sauerwein, H. (2023) · Journal of Dairy Science · doi:10.3168/jds.2023-23572 · Cited by 11
Hamuro, J., Deguchi, H., Fujita, T., Ueda, K., Tokuda, Y., Hiramoto, N., Numa, K., Nakano, M., Bush, J., Ueno, M., et al. (2020) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.61.5.47 · Cited by 11
“Considering the recent identification of SLC12A8 as an NMN transporter and the requirement of sodium ion for the transport, 18 SLC12A8 may play a critical role in regulating NAD + , as well as in cHCECs.”
InfluentialSong, M., Yin, C., Xu, Q., Liu, Y., Zhang, H., Liu, X., & Yan, H. (2023) · Foods · doi:10.3390/foods12152897 · Cited by 11
“Above all, the oral administration of NMN can effectively compensate for poor absorption through the direct feeding of NAD+, where NMN crosses the cell membrane by active transport and is then converted into NAD+ in human cells [4].”
BackgroundMetabolism and Receptor Mechanisms of Niacin Action
Boronovskiy, S. E., Сергеевна, К. В., & Nartsissov, Y. R. (2024) · Cell and Tissue Biology · doi:10.1134/s1990519x23700025 · Cited by 12
“It should be noted that there is an experimentally substantiated hypothesis according to which NMN can act as an extracellular precursor of NAD, entering the cell directly through the specific transporter SLC12A8 (Grozio et al., 2019).”
Takeda, K., & Okumura, K. (2021) · Biomedical Research · doi:10.2220/biomedres.42.173 · Cited by 11
“It was reported that NMN is rapidly absorbed through a transporter in the small intestine and orally administered NMN is quickly utilized to synthesize NAD+ in tissues (Grozio et al. 2019).”
BackgroundPrioritization of genes associated with type 2 diabetes mellitus for functional studies
Tan, W. X., Sim, X., Khoo, C. M., & Teo, A. K. K. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00836-1 · Cited by 10
SLC12A8 mediates TKI resistance in EGFR-mutant lung cancer via PDK1/AKT axis
Huang, F., Cui, J., Wan, J., Yuan, X., Zhu, Y., Wu, X., Zuo, W., & Zhao, T. (2023) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-023-05416-4 · Cited by 11
“Apart from its role in drug response regulation, SLC12A8 has been identified as a transporter for nicotinamide mononucleotide (NMN), a crucial molecule involved in nicotinamide adenine dinucleotide (NAD +)-mediated energy metabolism (Grozio et al. 2019).”
BackgroundAntizyme inhibitor family: biological and translational research implications
Feng, Q., Wang, H., Shao, Y.-C., & Xu, X. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01445-1 · Cited by 10
“For example, ATP13A2 has been shown to be a lysosomal polyamine exporter [66], and SLC12A8 was originally regarded as another polyamine importer [67], but now is designated as an amino-acid and a nicotinamide mononucleotide transporter [68].”
BackgroundShen, J., Xu, F., Liu, T., Ye, Y., & Xu, S. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07939-9 · Cited by 13
“Elevated NAD + levels suppress SURF4 expression, promoting STING stabilization at the Golgi apparatus and thereby enhancing p-STING/p-IRF3 axis-mediated T cell activation.”
NAD+ oscillation and hypothalamic neuronal functions
Tokizane, K., & Imai, S. (2021) · Faculty Reviews · doi:10.12703/r/10-42 · Cited by 10
Self-citationQiu, S., Zhang, Y., 邵诗涵, Zhang, Y., Yin, J., Xu, X., Yang, J. J., Hong, Y., Yang, J., Tan, X., et al. (2024) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2024.101655 · Cited by 12
“In contrast, it has also been reported that NMN can be directly transported into cells via a transporter coded by the SLC12A8 gene in the intestine of mice [28].”
BackgroundDoig, C. L., Zielinska, A. E., Fletcher, R. S., Oakey, L. A., Elhassan, Y., Garten, A., Cartwright, D., Heising, S., Alsheri, A., Watson, D. G., et al. (2020) · Skeletal Muscle · doi:10.1186/s13395-019-0216-z · Cited by 13
Liu, J., Huo, R., Fu, H., Chen, S., Qiao, X., Xu, B., Zhang, Z., Wu, J., & Su, L. (2024) · Enzyme and Microbial Technology · doi:10.1016/j.enzmictec.2024.110482 · Cited by 9
Quantitative dynamics of intracellular NMN by genetically encoded biosensor
Chen, L., Wang, P., Huang, G., Cheng, W., Liu, K., & Yu, Q. (2024) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2024.116842 · Cited by 9
Tanabe, K., Zheng, Q., Zhang, X., Tanaka, N., Hayashi, C., Yokota, A., Otsuka, R., Katahira, T., Kohjima, M., & Nakamuta, M. (2025) · Scientific Reports · doi:10.1038/s41598-025-04670-5 · Cited by 11
“Moreover, the significant decrease in NMN levels in the plasma suggests that Slc12a8, the transporter of NMN 37 in ZDF rat hearts may have been activated, resulting in the influx of NMN from blood into the cardiomyocytes of ZDF rats.”
InfluentialSynthesis of Mixed Dinucleotides by Mechanochemistry
Hayat, F., Makarov, M. V., Belfleur, L., & Migaud, M. E. (2022) · Molecules · doi:10.3390/molecules27103229 · Cited by 9
Self-citationNAD in pathological cardiac remodeling: Metabolic regulation and beyond
Norambuena‐Soto, I., Deng, Y., Brenner, C., Lavandero, S., & Wang, Z. V. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167038 · Cited by 9
Chen, F., Zhou, D., Kong, A. P.-S., Yim, N. T., Dai, S., Chen, Y., & Hui, L. L. (2024) · Current Diabetes Reports · doi:10.1007/s11892-024-01557-z · Cited by 8
“However the uptake pathway of NMN in cells and tissues is still controversial, [12, 13] and thus it is not clear whether oral supplementation of NMN in humans improves glucose control and lipid profile.”
CD38 mediates nicotinamide mononucleotide base exchange to yield nicotinic acid mononucleotide
Madawala, R. J., Banks, J. L., Hancock, S. E., Quek, L., Turner, N. A., & Wu, L. E. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108248 · Cited by 9
“NMN enters the cell following its extracellular dephosphorylation into NR (61) and its incorporation into the NAD + metabolome is blocked by deletion of NRK enzymes (62), with controversy around the existence of an intact NMN transporter (63 – 65).”
Programmed axon degeneration: mechanism, inhibition and therapeutic potential
Loreto, A., & Neukomm, L. J. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00986-3 · Cited by 8
“NMN requires a transmembrane transporter to enter neurons, although its putative transporter is currently debated 118–120 .”
Senescence-associated metabolic alterations aggravate calcific aortic valve disease
Qian, X., Xu, L., Zheng, Y., Fan, Z., Jiang, C., Liu, Y., Tong, F., Fan, P., Chen, M., Chen, Z., et al. (2026) · European Heart Journal · doi:10.1093/eurheartj/ehag191 · Cited by 8
Recent Advances in the Chemical Synthesis of β-Nicotinamide Mononucleotide
Ming, W., Hu, S., Liu, Y., Li, Q.-A.-W., Zhu, Y., & Gu, S.-X. (2023) · Current Organic Chemistry · doi:10.2174/1385272827666230201103848 · Cited by 9
Miao, C., Zheng, S., Wang, D., Dong, X. W., Guan, Y., Qi, Q., Hu, W., Hong, C., & Zhang, C. (2022) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201023666220518113219 · Cited by 8
Nicotinamide mononucleotide, a potential future treatment in ocular diseases
Lee, D., Tomita, Y., Shinojima, A., Ban, N., Yamaguchi, S., Nishioka, K., Negishi, K., Yoshino, J., & Kurihara, T. (2023) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-023-06118-w · Cited by 8
“NMN is one of the intermediates in nicotinamide adenine dinucleotide (NAD + ) biosynthesis [1–5].”
Self-citationNAD+ Precursors Reverse Experimental Diabetic Neuropathy in Mice
Chandrasekaran, K., Najimi, N., Sagi, A. R., Yarlagadda, S., Salimian, M., Arvas, M. I., Hedayat, A. F., Kevas, Y., Kadakia, A., Kristián, T., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021102 · Cited by 7
Is N1-Methylnicotinamide a Good Organic Cation Transporter 2 (OCT2) Biomarker?
Ailabouni, A. S., Vijaywargi, G., Subash, S., Singh, D. K., Gáborik, Z., & Prasad, B. (2025) · Metabolites · doi:10.3390/metabo15020080 · Cited by 7
Cordone, V., Vergara, T., Falone, S., Tatone, C., & Emidio, G. D. (2025) · Biology of Reproduction · doi:10.1093/biolre/ioaf140 · Cited by 8
Nicotinamide riboside kinase 1 protects against diet and age-induced pancreatic β-cell failure
Cercillieux, A., Ratajczak, J., Joffraud, M., Sanchez-Garcia, J. L., Jacot, G. E., Zollinger, A., Métairon, S., Giroud‐Gerbetant, J., Rumpler, M., Ciarlo, E., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101605 · Cited by 10
Differences in Extracellular NAD+ and NMN Metabolism on the Surface of Vascular Endothelial Cells
Jabłońska, P., Mierzejewska, P., Tomczyk, M., Koszałka, P., Frańczak, M., Kawecka, A., Kutryb-Zając, B. A., Braczko, A., Smolenski, R. T., & Slominska, E. M. (2022) · Biology · doi:10.3390/biology11050675 · Cited by 7
“Moreover, interest in this compound is growing since the plasma transporter for NMN has been recently discovered [30], although not all approve of this finding [31].”
BackgroundZhang, J., Poon, E. T., & Wong, S. H. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2024.2387324 · Cited by 6
“A newly identified gene, Slc12a8 , which is highly expressed in the small intestine, has been proposed as a potentially promising NMN transporter (Grozio et al. 2019).”
Metadata
- Authors
- Grozio, A., Mills, K. F., Yoshino, J., Bruzzone, S., Sociali, G., Tokizane, K., Lei, H. C., Cunningham, R., Sasaki, Y., Migaud, M. E., & Imai, S.-I.
- Affiliations
- Washington University in St. Louis (US)
- University of Genoa (IT)
- USA Mitchell Cancer Institute (US)
- Corresponding author
- Imai, Shin-ichiro
- ORCID
- Venue
- Nature Metabolism
- Published
- 2019-01-07
- Volume
- 1
- Issue
- 1
- Pages
- 47-57
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC6530925
- OpenAlex
- W2903854778
- Cited by
- 287
- References
- 48
- Citations by year
- 2026: 33 · 2025: 37 · 2024: 41 · 2023: 48 · 2022: 39 · 2021: 33 · 2020: 31 · 2019: 22
- FWCI
- 12.04
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-07-12)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- National Institutes of Health (1c06rr015502-01, UL1TR002345)
- Biotechnology and Biological Sciences Research Council (BB/N001842/1)
- National Institute on Aging (R01AG024150, R01AG037457, R01AG047902)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056341, P30DK020579)
- National Center for Research Resources (C06-RR-015502)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- NAD+ metabolism, small intestine, sodium-dependent transport, aging, nicotinamide riboside, NAD biosynthesis
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