{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:42:35Z","timestamp":1785213755246,"version":"3.55.0"},"reference-count":91,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["I01 BX001340 to BSK,2I01 BX000926 to GGC,IK6BX00361 to GGC,1I01BX003234 to KS"],"award-info":[{"award-number":["I01 BX001340 to BSK,2I01 BX000926 to GGC,IK6BX00361 to GGC,1I01BX003234 to KS"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,8]]},"abstract":"<jats:p>The role of insulin receptor (IR) activated by hyperinsulinemia in obesity-induced kidney injury is not well understood. We hypothesized that activation of kidney proximal tubule epithelial IR contributes to obesity-induced kidney injury. We administered normal-fat diet (NFD) or high-fat diet (HFD) to control and kidney proximal tubule IR\u2013knockout (KPTIRKO) mice for 4 months. Renal cortical IR expression was decreased by 60% in male and female KPTIRKO mice. Baseline serum glucose, serum creatinine, and the ratio of urinary albumin to creatinine (ACR) were similar in KPTIRKO mice compared to those of controls. On HFD, weight gain and increase in serum cholesterol were similar in control and KPTIRKO mice; blood glucose did not change. HFD increased the following parameters in the male control mice: renal cortical contents of phosphorylated IR and Akt, matrix proteins, urinary ACR, urinary kidney injury molecule-1\u2013to-creatinine ratio, and systolic blood pressure. Renal cortical generation of hydrogen sulfide was reduced in HFD-fed male control mice. All of these parameters were ameliorated in male KPTIRKO mice. Interestingly, female mice were resistant to HFD-induced kidney injury in both genotypes. We conclude that HFD-induced kidney injury requires renal proximal tubule IR activation in male mice.<\/jats:p>","DOI":"10.1172\/jci.insight.143619","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T13:25:52Z","timestamp":1609853152000},"source":"Crossref","is-referenced-by-count":22,"title":["Proximal tubular epithelial insulin receptor mediates high-fat diet\u2013induced kidney injury"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3954-3216","authenticated-orcid":true,"given":"Hak Joo","family":"Lee","sequence":"first","affiliation":[{"name":"Center for Renal Medicine, Division of Nephrology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenalakshmi M.","family":"Mariappan","sequence":"additional","affiliation":[{"name":"Center for Renal Medicine, Division of Nephrology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0231-5722","authenticated-orcid":true,"given":"Luke","family":"Norton","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Bakewell","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Feliers","sequence":"additional","affiliation":[{"name":"Center for Renal Medicine, Division of Nephrology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae Byeol","family":"Oh","sequence":"additional","affiliation":[{"name":"Center for Renal Medicine, Division of Nephrology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Donati","sequence":"additional","affiliation":[{"name":"Center for Renal Medicine, Division of Nephrology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8448-0827","authenticated-orcid":true,"given":"Cherubina S.","family":"Rubannelsonkumar","sequence":"additional","affiliation":[{"name":"Center for Renal Medicine, Division of Nephrology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjeri A.","family":"Venkatachalam","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen E.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Periodontics, University of Texas Health, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4267-6207","authenticated-orcid":true,"given":"Isabelle","family":"Rubera","sequence":"additional","affiliation":[{"name":"Universite Cote d\u2019Azur, CNRS \u2013 UMR-7370, Laboratoire de Physiom\u00e9decine Mol\u00e9culaire, Nice, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8383-9818","authenticated-orcid":true,"given":"Michel","family":"Tauc","sequence":"additional","affiliation":[{"name":"Universite Cote d\u2019Azur, CNRS \u2013 UMR-7370, Laboratoire de Physiom\u00e9decine Mol\u00e9culaire, Nice, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goutam","family":"Ghosh Choudhury","sequence":"additional","affiliation":[{"name":"Center for Renal Medicine, Division of Nephrology,"},{"name":"VA Research and"},{"name":"Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7583-9228","authenticated-orcid":true,"given":"C. 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