{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T20:18:08Z","timestamp":1784665088109,"version":"3.55.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Metab"],"DOI":"10.1038\/s42255-024-01206-5","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T10:02:07Z","timestamp":1737021727000},"page":"367-382","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Proline exacerbates hepatic gluconeogenesis via paraspeckle-dependent mRNA retention"],"prefix":"10.1038","volume":"7","author":[{"given":"Yurong","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxuan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linghao","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sishuo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzhou","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7669-9506","authenticated-orcid":false,"given":"Chi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1207-7449","authenticated-orcid":false,"given":"Jinghao","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"1206_CR1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","volume":"402","author":"GBD 2021 Diabetes Collaborators.","year":"2023","unstructured":"GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 402, 203\u2013234 (2023).","journal-title":"Lancet"},{"key":"1206_CR2","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.tem.2017.03.003","volume":"28","author":"PM Titchenell","year":"2017","unstructured":"Titchenell, P. M., Lazar, M. A. & Birnbaum, M. J. Unraveling the regulation of hepatic metabolism by insulin. Trends Endocrinol. Metab. 28, 497\u2013505 (2017).","journal-title":"Trends Endocrinol. Metab."},{"key":"1206_CR3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.cmet.2011.06.003","volume":"14","author":"HV Lin","year":"2011","unstructured":"Lin, H. V. & Accili, D. Hormonal regulation of hepatic glucose production in health and disease. Cell Metab. 14, 9\u201319 (2011).","journal-title":"Cell Metab."},{"key":"1206_CR4","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/nrd.2016.151","volume":"15","author":"AK Rines","year":"2016","unstructured":"Rines, A. K., Sharabi, K., Tavares, C. D. & Puigserver, P. Targeting hepatic glucose metabolism in the treatment of type 2 diabetes. Nat. Rev. Drug Discov. 15, 786\u2013804 (2016).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1206_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100727","volume":"3","author":"S Wang","year":"2022","unstructured":"Wang, S. et al. Amino acids, microbiota-related metabolites, and the risk of incident diabetes among normoglycemic Chinese adults: findings from the 4C study. Cell Rep. Med. 3, 100727 (2022).","journal-title":"Cell Rep. Med."},{"key":"1206_CR6","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.2337\/dc21-1705","volume":"45","author":"J Morze","year":"2022","unstructured":"Morze, J. et al. Metabolomics and type 2 diabetes risk: an updated systematic review and meta-analysis of prospective cohort studies. Diabetes Care 45, 1013\u20131024 (2022).","journal-title":"Diabetes Care"},{"key":"1206_CR7","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/s41586-022-05637-6","volume":"614","author":"MK Handzlik","year":"2023","unstructured":"Handzlik, M. K. et al. Insulin-regulated serine and lipid metabolism drive peripheral neuropathy. Nature 614, 118\u2013124 (2023).","journal-title":"Nature"},{"key":"1206_CR8","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.cmet.2009.02.002","volume":"9","author":"CB Newgard","year":"2009","unstructured":"Newgard, C. B. et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 9, 311\u2013326 (2009).","journal-title":"Cell Metab."},{"key":"1206_CR9","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/s42255-021-00369-9","volume":"3","author":"JG Okun","year":"2021","unstructured":"Okun, J. G. et al. Liver alanine catabolism promotes skeletal muscle atrophy and hyperglycaemia in type 2 diabetes. Nat. Metab. 3, 394\u2013409 (2021).","journal-title":"Nat. Metab."},{"key":"1206_CR10","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.celrep.2014.09.030","volume":"9","author":"G Gheni","year":"2014","unstructured":"Gheni, G. et al. Glutamate acts as a key signal linking glucose metabolism to incretin\/cAMP action to amplify insulin secretion. Cell Rep. 9, 661\u2013673 (2014).","journal-title":"Cell Rep."},{"key":"1206_CR11","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1042\/EBC20200010","volume":"64","author":"Y Wang","year":"2020","unstructured":"Wang, Y. & Chen, L. L. Organization and function of paraspeckles. Essays Biochem. 64, 875\u2013882 (2020).","journal-title":"Essays Biochem."},{"key":"1206_CR12","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/j.molcel.2009.01.026","volume":"33","author":"CM Clemson","year":"2009","unstructured":"Clemson, C. M. et al. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol. Cell 33, 717\u2013726 (2009).","journal-title":"Mol. Cell"},{"key":"1206_CR13","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/s41556-018-0204-2","volume":"20","author":"Y Wang","year":"2018","unstructured":"Wang, Y. et al. Genome-wide screening of NEAT1 regulators reveals cross-regulation between paraspeckles and mitochondria. Nat. Cell Biol. 20, 1145\u20131158 (2018).","journal-title":"Nat. Cell Biol."},{"key":"1206_CR14","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1093\/nar\/gkab1216","volume":"50","author":"GJ Knott","year":"2022","unstructured":"Knott, G. J. et al. Structural basis of dimerization and nucleic acid binding of human DBHS proteins NONO and PSPC1. Nucleic Acids Res. 50, 522\u2013535 (2022).","journal-title":"Nucleic Acids Res."},{"key":"1206_CR15","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.3390\/biomedicines9091148","volume":"9","author":"M Kaare","year":"2021","unstructured":"Kaare, M. et al. High-fat diet induces pre-diabetes and distinct sex-specific metabolic alterations in Negr1-deficient mice. Biomedicines 9, 1148 (2021).","journal-title":"Biomedicines"},{"key":"1206_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.109251","volume":"113","author":"H Guo","year":"2023","unstructured":"Guo, H. et al. Oat beta-glucan ameliorates diabetes in high fat diet and streptozotocin-induced mice by regulating metabolites. J. Nutr. Biochem. 113, 109251 (2023).","journal-title":"J. Nutr. Biochem."},{"key":"1206_CR17","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cca.2010.12.023","volume":"412","author":"H Tsutsui","year":"2011","unstructured":"Tsutsui, H. et al. Biomarker discovery in biological specimens (plasma, hair, liver and kidney) of diabetic mice based upon metabolite profiling using ultra-performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry. Clin. Chim. Acta 412, 861\u2013872 (2011).","journal-title":"Clin. Chim. Acta"},{"key":"1206_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14323-y","volume":"11","author":"M Pradas-Juni","year":"2020","unstructured":"Pradas-Juni, M. et al. A MAFG\u2013lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism. Nat. Commun. 11, 644 (2020).","journal-title":"Nat. Commun."},{"key":"1206_CR19","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41580-021-00330-4","volume":"22","author":"L Statello","year":"2021","unstructured":"Statello, L., Guo, C. J., Chen, L. L. & Huarte, M. Author correction: gene regulation by long non-coding RNAs and its biological functions. Nat. Rev. Mol. Cell Biol. 22, 159 (2021).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1206_CR20","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1007\/s00018-020-03632-6","volume":"78","author":"A Naveed","year":"2021","unstructured":"Naveed, A. et al. NEAT1 polyA-modulating antisense oligonucleotides reveal opposing functions for both long non-coding RNA isoforms in neuroblastoma. Cell. Mol. Life Sci. 78, 2213\u20132230 (2021).","journal-title":"Cell. Mol. Life Sci."},{"key":"1206_CR21","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.tplants.2021.07.009","volume":"27","author":"ME Alvarez","year":"2022","unstructured":"Alvarez, M. E., Savoure, A. & Szabados, L. Proline metabolism as regulatory hub. Trends Plant Sci. 27, 39\u201355 (2022).","journal-title":"Trends Plant Sci."},{"key":"1206_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121402","volume":"316","author":"J Turbitt","year":"2023","unstructured":"Turbitt, J. et al. NKCC transport mediates the insulinotropic effects of taurine and other small neutral amino acids. Life Sci. 316, 121402 (2023).","journal-title":"Life Sci."},{"key":"1206_CR23","doi-asserted-by":"publisher","first-page":"dgz240","DOI":"10.1210\/clinem\/dgz240","volume":"105","author":"Y Sun","year":"2020","unstructured":"Sun, Y., Gao, H. Y., Fan, Z. Y., He, Y. & Yan, Y. X. Metabolomics signatures in type 2 diabetes: a systematic review and integrative analysis. J. Clin. Endocrinol. Metab. 105, dgz240 (2020).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"1206_CR24","doi-asserted-by":"publisher","first-page":"833","DOI":"10.2337\/dc15-2251","volume":"39","author":"M Guasch-Ferre","year":"2016","unstructured":"Guasch-Ferre, M. et al. Metabolomics in prediabetes and diabetes: a systematic review and meta-analysis. Diabetes Care 39, 833\u2013846 (2016).","journal-title":"Diabetes Care"},{"key":"1206_CR25","doi-asserted-by":"publisher","first-page":"e1003112","DOI":"10.1371\/journal.pmed.1003112","volume":"17","author":"M Lai","year":"2020","unstructured":"Lai, M. et al. Amino acid and lipid metabolism in post-gestational diabetes and progression to type 2 diabetes: a metabolic profiling study. PLoS Med. 17, e1003112 (2020).","journal-title":"PLoS Med."},{"key":"1206_CR26","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.1016\/j.numecd.2021.05.004","volume":"31","author":"Y Chen","year":"2021","unstructured":"Chen, Y. et al. Associations between serum amino acids and incident type 2 diabetes in Chinese rural adults. Nutr. Metab. Cardiovasc. Dis. 31, 2416\u20132425 (2021).","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"1206_CR27","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1530\/JME-16-0116","volume":"57","author":"F Xiao","year":"2016","unstructured":"Xiao, F. et al. Effects of essential amino acids on lipid metabolism in mice and humans. J. Mol. Endocrinol. 57, 223\u2013231 (2016).","journal-title":"J. Mol. Endocrinol."},{"key":"1206_CR28","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12199-017-0642-7","volume":"22","author":"N Yamaguchi","year":"2017","unstructured":"Yamaguchi, N. et al. Plasma free amino acid profiles evaluate risk of metabolic syndrome, diabetes, dyslipidemia, and hypertension in a large Asian population. Environ. Health Prev. Med 22, 35 (2017).","journal-title":"Environ. Health Prev. Med"},{"key":"1206_CR29","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2020-001315","volume":"8","author":"SH Gunther","year":"2020","unstructured":"Gunther, S. H. et al. Serum acylcarnitines and amino acids and risk of type 2 diabetes in a multiethnic Asian population. BMJ Open Diabetes Res. Care 8, e001315 (2020).","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"1206_CR30","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1007\/s00125-009-1637-8","volume":"53","author":"ES Tai","year":"2010","unstructured":"Tai, E. S. et al. Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men. Diabetologia 53, 757\u2013767 (2010).","journal-title":"Diabetologia"},{"key":"1206_CR31","doi-asserted-by":"publisher","first-page":"791","DOI":"10.2337\/db13-0396","volume":"63","author":"AE Thalacker-Mercer","year":"2014","unstructured":"Thalacker-Mercer, A. E. et al. BMI, RQ, diabetes, and sex affect the relationships between amino acids and clamp measures of insulin action in humans. Diabetes 63, 791\u2013800 (2014).","journal-title":"Diabetes"},{"key":"1206_CR32","doi-asserted-by":"publisher","first-page":"4127","DOI":"10.1083\/jcb.201904098","volume":"218","author":"H An","year":"2019","unstructured":"An, H., Tan, J. T. & Shelkovnikova, T. A. Stress granules regulate stress-induced paraspeckle assembly. J. Cell Biol. 218, 4127\u20134140 (2019).","journal-title":"J. Cell Biol."},{"key":"1206_CR33","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.cmet.2017.12.010","volume":"27","author":"G Benegiamo","year":"2018","unstructured":"Benegiamo, G. et al. The RNA-binding protein NONO coordinates hepatic adaptation to feeding. Cell Metab. 27, 404\u2013418 (2018).","journal-title":"Cell Metab."},{"key":"1206_CR34","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","volume":"98","author":"MC Petersen","year":"2018","unstructured":"Petersen, M. C. & Shulman, G. I. Mechanisms of insulin action and insulin resistance. Physiol. Rev. 98, 2133\u20132223 (2018).","journal-title":"Physiol. Rev."},{"key":"1206_CR35","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1038\/nmeth.2598","volume":"10","author":"ML Maeder","year":"2013","unstructured":"Maeder, M. L. et al. CRISPR RNA-guided activation of endogenous human genes. Nat. Methods 10, 977\u2013979 (2013).","journal-title":"Nat. Methods"},{"key":"1206_CR36","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1016\/j.cmet.2021.04.006","volume":"33","author":"YX Ji","year":"2021","unstructured":"Ji, Y. X. et al. A kinome screen reveals that Nemo-like kinase is a key suppressor of hepatic gluconeogenesis. Cell Metab. 33, 1171\u20131186 e1179 (2021).","journal-title":"Cell Metab."},{"key":"1206_CR37","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.tips.2012.04.005","volume":"33","author":"N Arnberg","year":"2012","unstructured":"Arnberg, N. Adenovirus receptors: implications for targeting of viral vectors. Trends Pharmacol. Sci. 33, 442\u2013448 (2012).","journal-title":"Trends Pharmacol. Sci."},{"key":"1206_CR38","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1016\/j.clinbiochem.2013.05.045","volume":"46","author":"Y Zhou","year":"2013","unstructured":"Zhou, Y. et al. Obesity and diabetes related plasma amino acid alterations. Clin. Biochem. 46, 1447\u20131452 (2013).","journal-title":"Clin. Biochem."},{"key":"1206_CR39","doi-asserted-by":"publisher","first-page":"4270","DOI":"10.2337\/db13-0570","volume":"62","author":"C Menni","year":"2013","unstructured":"Menni, C. et al. Biomarkers for type 2 diabetes and impaired fasting glucose using a nontargeted metabolomics approach. Diabetes 62, 4270\u20134276 (2013).","journal-title":"Diabetes"},{"key":"1206_CR40","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1093\/ije\/dyw221","volume":"45","author":"G Qiu","year":"2016","unstructured":"Qiu, G. et al. Plasma metabolomics identified novel metabolites associated with risk of type 2 diabetes in two prospective cohorts of Chinese adults. Int. J. Epidemiol. 45, 1507\u20131516 (2016).","journal-title":"Int. J. Epidemiol."},{"key":"1206_CR41","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1007\/s00125-016-4069-2","volume":"59","author":"Y Lu","year":"2016","unstructured":"Lu, Y. et al. Metabolic signatures and risk of type 2 diabetes in a Chinese population: an untargeted metabolomics study using both LC\u2013MS and GC\u2013MS. Diabetologia 59, 2349\u20132359 (2016).","journal-title":"Diabetologia"},{"key":"1206_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/srep46337","volume":"7","author":"VD de Mello","year":"2017","unstructured":"de Mello, V. D. et al. Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study. Sci. Rep. 7, 46337 (2017).","journal-title":"Sci. Rep."}],"container-title":["Nature Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42255-024-01206-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-024-01206-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-024-01206-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T23:02:53Z","timestamp":1740524573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42255-024-01206-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,16]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["1206"],"URL":"https:\/\/doi.org\/10.1038\/s42255-024-01206-5","relation":{},"ISSN":["2522-5812"],"issn-type":[{"value":"2522-5812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,16]]},"assertion":[{"value":"15 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}