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The efficacy of pyruvate supplementation in diabetic retinopathy and nephropathy has been shown in animal models; however, its significance in the functional maintenance of neurons and Schwann cells under diabetic conditions remains unknown. We observed rapid and extensive cell death under high-glucose (&gt;\u200910\u00a0mM) and pyruvate-starved conditions. Exposure of Schwann cells to these conditions led to a significant decrease in glycolytic flux, mitochondrial respiration and ATP production, accompanied by enhanced collateral glycolysis pathways (e.g., polyol pathway). Cell death could be prevented by supplementation with 2-oxoglutarate (a TCA cycle intermediate), benfotiamine (the vitamin B1 derivative that suppresses the collateral pathways), or the poly (ADP-ribose) polymerase (PARP) inhibitor, rucaparib. Our findings suggest that exogenous pyruvate plays a pivotal role in maintaining glycolysis\u2013TCA cycle flux and ATP production under high-glucose conditions by suppressing PARP activity.<\/jats:p>","DOI":"10.1038\/s41598-021-98082-w","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T10:57:49Z","timestamp":1632394669000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Role of pyruvate in maintaining cell viability and energy production under high-glucose conditions"],"prefix":"10.1038","volume":"11","author":[{"given":"Hideji","family":"Yako","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Niimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuka","family":"Takaku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuaki","family":"Tatsumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumasa","family":"Nishito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Sango","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"98082_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/j.2040-1124.2010.00070.x","volume":"2","author":"S Yagihashi","year":"2011","unstructured":"Yagihashi, S., Mizukami, H. & Sugimoto, K. 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