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These signalling metabolites, often derived from nutrients, the gut microbiota or the host\u2019s intermediary metabolism, are now acknowledged as key regulators of various metabolic and immune responses. This review delves into the multi-dimensional aspects of succinate, a dual metabolite with roots in both the mitochondria and microbiome. It also connects the dots between succinate\u2019s role in the Krebs cycle, mitochondrial respiration, and its double-edge function as a signalling transmitter within and outside the cell. We aim to provide an overview of the role of the succinate\u2013succinate receptor 1 (SUCNR1) axis in diabetes, discussing the potential use of succinate as a biomarker and the novel prospect of targeting SUCNR1 to manage complications associated with diabetes. We further propose strategies to manipulate the succinate\u2013SUCNR1 axis for better diabetes management; this includes pharmacological modulation of SUCNR1 and innovative approaches to manage succinate concentrations, such as succinate administration and indirect strategies, like microbiota modulation. The dual nature of succinate, both in terms of origins and roles, offers a rich landscape for understanding the intricate connections within metabolic diseases, like diabetes, and indicates promising pathways for developing new therapeutic strategies.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00125-023-06063-7","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T19:02:21Z","timestamp":1704481341000},"page":"430-442","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Type 2 diabetes and succinate: unmasking an age-old molecule"],"prefix":"10.1007","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-3788","authenticated-orcid":false,"given":"Sonia","family":"Fern\u00e1ndez-Veledo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-6522","authenticated-orcid":false,"given":"Anna","family":"Marsal-Beltran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6994-6115","authenticated-orcid":false,"given":"Joan","family":"Vendrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"issue":"9","key":"6063_CR1","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/J.TEM.2021.06.003","volume":"32","author":"S Fern\u00e1ndez-Veledo","year":"2021","unstructured":"Fern\u00e1ndez-Veledo S, Ceperuelo-Mallafr\u00e9 V, Vendrell J (2021) Rethinking succinate: an unexpected hormone-like metabolite in energy homeostasis. 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In particular, we acknowledge J. Sabadell-Basallote (Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA) for the assistance with figure design.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Research in the authors\u2019 laboratory is supported by grants from the Spanish Ministry of Science and Innovation MCIN\/AEI\/10.13039\/ 501100011033 (RTI2018-093919-B-100 and PID2021-122480OB-100 to SF-V), from the Instituto de Salud Carlos III (ISCIII) (PI20\/00338 to JV), all co-financed by the European Regional Development Fund (ERDF), and from CIBER -Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CB07708\/0012), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaci\u00f3n. Work in the authors\u2019 laboratory also received financial support from \"La Caixa\" Foundation (ID 100010434) under grant agreement LCF\/PR\/HR20\/52400013 (to SF-V). Both SF-V and JV acknowledge support from the Agency for Management of University Research Grants of the Generalitat de Catalunya (2021 SGR 01409, 2021 SGR 0089). AM-B is a recipient of an FPU grant (FPU20\/05633) from MCIN\/AEI\/10.13039\/501100011033.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"SF-V and JV are co-founders of SucciPro, S.L. No aspect of this article has been influenced by this relationship, nor is there any perceived influence on the work. All authors declare that there are no relevant relationships or activities that could bias, or be perceived to bias, their research efforts.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author\u2019s relationships and activities"}},{"value":"SF-V designed and conceived the outline of this review. SF-V and AM-B wrote the original draft. SF-V, AM-B and JV reviewed and edited the manuscript. All authors approved the final manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}