{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:16:59Z","timestamp":1783311419687,"version":"3.54.6"},"reference-count":29,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2023J01091"],"award-info":[{"award-number":["2023J01091"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joint Funds for the Innovation of Science and Technology, Fujian Province","award":["2025Y9133"],"award-info":[{"award-number":["2025Y9133"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role of gluconeogenesis in kidney disease has increasingly drawn attention. Fructose-1,6-bisphosphatase 1 (FBP1) is a key rate-limiting enzyme in gluconeogenesis that suppresses glycolysis and reduces lactate production. In this study, we first analyzed public transcriptomic datasets of diabetic kidney disease (DKD) and validated the findings in 24-week-old BKS-db mice and in high-glucose-induced human renal tubular epithelial (HK-2) cells. We further constructed tubular-specific FBP1 overexpression\/knockdown mouse models via adeno-associated virus serotype 9 (AAV-9) and combined pharmacological inhibition of lactate dehydrogenase B (LDHB) to dissect the underlying mechanism. Analysis of public clinical transcriptomic datasets showed that renal tubular FBP1 expression was positively correlated with estimated glomerular filtration rate (eGFR). In vivo, tubular-specific FBP1 overexpression in BKS-db mice reduced 24-h urinary protein and decreased renal lactate accumulation (p &lt; 0.05) compared with diabetic controls. In vitro, high glucose-induced lactate elevation in HK-2 cells was reversed by FBP1 overexpression, while co-treatment with an LDHB inhibitor abolished this protective effect. Our findings suggest that FBP1 represents a potential experimental therapeutic target associated with alleviation of renal lactic acid accumulation and mitochondrial injury in preclinical DKD models.<\/jats:p>","DOI":"10.3390\/ijms27135906","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:50:37Z","timestamp":1782867037000},"page":"5906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FBP1 Is Associated with Attenuated Mitochondrial Injury in Renal Tubular Epithelial Cells of Diabetic Kidney Disease via Modulation of Lactate Metabolism"],"prefix":"10.3390","volume":"27","author":[{"given":"Siyi","family":"Rao","sequence":"first","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyu","family":"You","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4298-9174","authenticated-orcid":false,"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, 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Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1053\/j.ackd.2017.10.011","article-title":"The Global Epidemiology of Diabetes and Kidney Disease","volume":"25","author":"Koye","year":"2018","journal-title":"Adv. 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Rheum. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5906\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:10:55Z","timestamp":1783311055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":29,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135906"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135906","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}