{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:29:06Z","timestamp":1790195346474,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The retinal pigment epithelium (RPE) contributes to retinal homeostasis, and its metabolic dysfunction is implied in the development of retinal degenerative disease. The isoform M2 of pyruvate kinase (PKM2) is a key factor in cell metabolism, and its function may be affected by insulin-like growth factor 1 (IGF-1). This study aims to investigate the effect of IGF-1 on PKM2 modulation of RPE cells and whether co-treatment with klotho may preserve it. ARPE-19 cells, an ex vivo model of human pigmented epithelium, were exposed to IGF-1. Then, we evaluated PKM2 expression, dimerization and subcellular localization, energy metabolism, and redox balance, and whether pre-treatment with Klotho may antagonize the effects of IGF-1. The results show that IGF-1 favors PKM2 dimerization, thus reducing the activity of PKM2 and leading to an altered cellular energy status coupled with reduced oxidative stress. In conclusion, PKM2 plays a pivotal role in the modulation of RPE metabolism and redox balance and could explain the mechanisms through which IGF-1 participates in the pathogenesis of some retinal diseases. Klotho may exert protective effects by mitigating the IGF-1 signal and its effect on mitochondrial function.<\/jats:p>","DOI":"10.3390\/ijms252413640","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T04:07:40Z","timestamp":1734667660000},"page":"13640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["IGF-1 Signaling Modulates Oxidative Metabolism and Stress Resistance in ARPE-19 Cells Through PKM2 Function"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0803-1042","authenticated-orcid":false,"given":"Silvia","family":"Ravera","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, Via De Toni 14, 16132 Genova, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9084-2636","authenticated-orcid":false,"given":"Alessandra","family":"Puddu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, University of Genova, Viale Benedetto XV 6, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4591-3260","authenticated-orcid":false,"given":"Nadia","family":"Bertola","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Verzola","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, University of Genova, Viale Benedetto XV 6, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1279-3178","authenticated-orcid":false,"given":"Elisa","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, University of Genova, Viale Benedetto XV 6, 16132 Genova, Italy"},{"name":"Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3928-1295","authenticated-orcid":false,"given":"Davide","family":"Maggi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, University of Genova, Viale Benedetto XV 6, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-1128","authenticated-orcid":false,"given":"Isabella","family":"Panfoli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014(DIFAR), University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100846","DOI":"10.1016\/j.preteyeres.2020.100846","article-title":"The Cell Biology of the Retinal Pigment Epithelium","volume":"78","author":"Lakkaraju","year":"2020","journal-title":"Prog. 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