{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:01:35Z","timestamp":1791050495911,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan","award":["JSPS KAKENHI 24K10032"],"award-info":[{"award-number":["JSPS KAKENHI 24K10032"]}]},{"name":"Scientific Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan","award":["20K16127"],"award-info":[{"award-number":["20K16127"]}]},{"name":"Scientific Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan","award":["2024047396"],"award-info":[{"award-number":["2024047396"]}]},{"name":"Takeda Science Foundation","award":["JSPS KAKENHI 24K10032"],"award-info":[{"award-number":["JSPS KAKENHI 24K10032"]}]},{"name":"Takeda Science Foundation","award":["20K16127"],"award-info":[{"award-number":["20K16127"]}]},{"name":"Takeda Science Foundation","award":["2024047396"],"award-info":[{"award-number":["2024047396"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus for which effective treatments remain undeveloped. Metabolic changes and inflammation are proposed as primary mechanisms underlying DPN pathogenesis. Our previous studies demonstrate that exogenous pyruvate plays a crucial role in maintaining glycolysis-tricarboxylic acid cycle flux under high-glucose conditions and also exhibits anti-inflammatory properties. To evaluate its therapeutic potential, we assessed whether pyruvate administration could restore DPN in vivo and in vitro. We assessed casual blood glucose levels, body weight, motor and sensory nerve conduction velocities, mechanical sensitivity, and intraepidermal nerve fiber density in streptozotocin-induced diabetic C57\/BL\/6J mice that received drinking water with or without sodium pyruvate (10 mg\/mL) from 2 to 13 weeks after diabetes induction. In addition, we evaluated neurite length in ND7\/23 cells, a dorsal root ganglion neuron cell line, under high-glucose conditions. Pyruvate administration in diabetic mice alleviated mechanical sensitivity deficits and improved intraepidermal nerve fiber density. Additionally, neurite length in ND7\/23 cells was inhibited under high-glucose conditions but was fully restored by supplementation with high concentrations (10 mM) of pyruvate. These findings suggest that exogenous pyruvate may be a promising therapeutic candidate for DPN.<\/jats:p>","DOI":"10.3390\/ijms26104666","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T11:31:49Z","timestamp":1747135909000},"page":"4666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pyruvate Administration Restores Impaired Nociception by Enhancing Neurite Outgrowth in Streptozotocin-Induced Diabetic Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2632-8488","authenticated-orcid":false,"given":"Hideji","family":"Yako","sequence":"first","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"},{"name":"Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0982, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7495-1675","authenticated-orcid":false,"given":"Mari","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8496-5181","authenticated-orcid":false,"given":"Shizuka","family":"Takaku","sequence":"additional","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Niimi","sequence":"additional","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Kato","sequence":"additional","affiliation":[{"name":"Laboratory of Medicine, School of Pharmacy, Aichi Gakuin University, Nagoya 470-0195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kato","sequence":"additional","affiliation":[{"name":"Laboratory of Medicine, School of Pharmacy, Aichi Gakuin University, Nagoya 470-0195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3618-998X","authenticated-orcid":false,"given":"Junji","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"},{"name":"Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0982, Japan"},{"name":"Laboratory of Molecular Pharmacology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9750-9596","authenticated-orcid":false,"given":"Kazunori","family":"Sango","sequence":"additional","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/jdi.14105","article-title":"Prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy in Japanese patients with type 2 diabetes: The Japan Diabetes Complication and its Prevention Prospective study (JDCP study 10)","volume":"15","author":"Kamiya","year":"2024","journal-title":"J. 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