{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:48:21Z","timestamp":1782535701365,"version":"3.54.5"},"reference-count":146,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The pleiotropic actions of insulin are mediated by cascades of signaling pathways and are regulated by circulating insulin levels. Under physiologic conditions, insulin levels reflect the balance between pancreatic beta-cell secretion and insulin clearance, which occurs primarily in liver hepatocytes and, to a lesser extent, in kidney proximal tubule cells. Therefore, coordination between insulin secretion and clearance is essential for systemic insulin sensitivity. Whereas insulin secretion is widely investigated, exploring the role of insulin clearance in regulating insulin sensitivity remains limited. This review summarizes the main mechanisms underlying insulin clearance along the liver\u2013kidney axis and discusses how they contribute to metabolic regulation in health and disease.<\/jats:p>","DOI":"10.3390\/metabo16070439","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:57:24Z","timestamp":1782287844000},"page":"439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Insulin Clearance Along the Liver\u2013Kidney Axis: Implications for Insulin Action"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2301-0012","authenticated-orcid":false,"given":"Germ\u00e1n","family":"Perdomo","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina y Gen\u00e9tica Molecular (Consejo Superior de Investigaciones Cient\u00edficas-Universidad de Valladolid), 47003 Valladolid, Spain"},{"name":"Instituto Biosanitario de Valladolid (IBioVALL), 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-5362","authenticated-orcid":false,"given":"Irene","family":"C\u00f3zar-Castellano","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Gen\u00e9tica Molecular (Consejo Superior de Investigaciones Cient\u00edficas-Universidad de Valladolid), 47003 Valladolid, Spain"},{"name":"Instituto Biosanitario de Valladolid (IBioVALL), 47003 Valladolid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6209-8902","authenticated-orcid":false,"given":"Sonia M.","family":"Najjar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Janssen, J. 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