{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:03:05Z","timestamp":1792843385688,"version":"4.5.0"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5P30-DK-036836,R01-DK- 053105"],"award-info":[{"award-number":["5P30-DK-036836,R01-DK- 053105"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["1DP3-DK-094333-01"],"award-info":[{"award-number":["1DP3-DK-094333-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"crossref","award":["9-18-CVD1-005"],"award-info":[{"award-number":["9-18-CVD1-005"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,8]]},"abstract":"<jats:p>\n                    Diabetic nephropathy (DN) arises from systemic and local changes in glucose metabolism and hemodynamics. We have reported that many glycolytic and mitochondrial enzymes, such as pyruvate kinase M2 (PKM2), were elevated in renal glomeruli of DN-protected patients with type 1 and type 2 diabetes. Here, mice with PKM2 overexpression specifically in podocytes (PPKM2Tg) were generated to uncover the renal protective function of PPKM2Tg as a potential therapeutic target that prevented elevated albumin\/creatinine ratio (ACR), mesangial expansion, basement membrane thickness, and podocyte foot process effacement after 7 months of streptozotocin-induced (STZ-induced) diabetes. Furthermore, diabetes-induced impairments of glycolytic rate and mitochondrial function were normalized in diabetic PPKM2Tg glomeruli, in concordance with elevated\n                    <jats:italic>Ppargc1a<\/jats:italic>\n                    and\n                    <jats:italic>Vegf<\/jats:italic>\n                    expressions. Restored VEGF expression improved glomerular maximal mitochondrial function in diabetic PPKM2Tg and WT mice. Elevated VEGF levels were observed in the glomeruli of DN-protected patients with chronic type 1 diabetes and clinically correlated with estimated glomerular filtration (GFR) \u2014 but not glycemic control. Mechanistically, the preservations of mitochondrial function and VEGF expression were dependent on tetrameric structure and enzymatic activities of PKM2 in podocytes. These findings demonstrate that PKM2 structure and enzymatic activation in podocytes can preserve the entire glomerular mitochondrial function against toxicity of hyperglycemia via paracrine factors such as VEGF and prevent DN progression.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.155260","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T12:06:27Z","timestamp":1644321987000},"source":"Crossref","is-referenced-by-count":50,"title":["Regeneration of glomerular metabolism and function by podocyte pyruvate kinase M2 in diabetic nephropathy"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4609-735X","authenticated-orcid":true,"given":"Jialin","family":"Fu","sequence":"first","affiliation":[{"name":"Dianne Nunnally Hoppes Laboratory for Diabetes Complications, Joslin Diabetes Center and"},{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, 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