{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T19:05:46Z","timestamp":1784574346906,"version":"3.55.0"},"reference-count":45,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"Zhengzhou Municipal Fundamental Research and Applied Basic Research Program","award":["2024ZZJCYJ001"],"award-info":[{"award-number":["2024ZZJCYJ001"]}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["No. 22ZR1414300"],"award-info":[{"award-number":["No. 22ZR1414300"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Thickening of the glomerular basement membrane (GBM) is one of the most common pathological changes in diabetic nephropathy (DN), but its underlying mechanisms remain unclear. Collagen \u03b11(IV) is predominantly expressed by endothelial cells and upregulated in the glomeruli in DN. Glucose transporter type 1 (GLUT1) serves as the primary transporter for glucose uptake in endothelial cells. This study demonstrates that GLUT1 and collagen \u03b11(IV) expression are both upregulated and positively correlated in glomerular endothelial cells (GECs) in DN. Inhibition of GLUT1 improved renal dysfunction and morphological abnormalities associated with DN progression in db\/db mice and streptozotocin-induced diabetic rat models. Mechanistically, GLUT1 promotes collagen \u03b11(IV) overexpression through activation of the Rheb\/mTORC1 pathway in GECs. In vitro studies revealed that O-GlcNAcylation of Rheb seems to mediate GLUT1-driven Rheb upregulation and subsequent mTORC1 activation. Collectively, these data establish the GLUT1-Rheb\/mTORC1\u2013collagen \u03b11(IV) axis in GECs, highlighting the pivotal role of GECs in mediating GBM thickening during DN pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>The role of glomerular endothelial cells in basement membrane collagen \u03b11(IV) accumulation in diabetic nephropathy was previously unclear. Glucose transporter type 1 (GLUT1) expression drives collagen \u03b11(IV) production via Rheb upregulation and mTORC1 activation. Rheb O-GlcNAcylation serves as a key modification that activates mTORC1 signaling, leading to increased collagen \u03b11(IV) production. Pharmacological inhibition of GLUT1 mitigates diabetic nephropathy progression, highlighting its therapeutic potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0883","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:37:39Z","timestamp":1780929459000},"page":"1437-1449","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of GLUT1 Ameliorates Thickening of the Glomerular Basement Membrane via the Rheb\/mTORC1 Pathway in Diabetic Nephropathy"],"prefix":"10.2337","volume":"75","author":[{"given":"Jitu","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Nephrology of Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Department of Pathology of the School of Basic Medical Sciences, Fudan University 1 , Shanghai, China"},{"name":"Institute of Nephrology, 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