{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:39:48Z","timestamp":1792813188139,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/610; PI20\/0690"],"award-info":[{"award-number":["PI18\/610; PI20\/0690"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CD19\/00055"],"award-info":[{"award-number":["CD19\/00055"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Agency for Administration of University and Research","doi-asserted-by":"publisher","award":["2020 GI_B1 00093"],"award-info":[{"award-number":["2020 GI_B1 00093"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin D (VD) deficiency has been associated with cancer and diabetes. Insulin signaling through the insulin receptor (IR) stimulates cellular responses by activating the PI3K\/AKT pathway. PTEN is a tumor suppressor and a negative regulator of the pathway. Its absence enhances insulin signaling leading to hypoglycemia, a dangerous complication found after insulin overdose. We analyzed the effect of VD signaling in a model of overactivation of the IR. We generated inducible double KO (DKO) mice for the VD receptor (VDR) and PTEN. DKO mice showed severe hypoglycemia, lower total cholesterol and increased mortality. No macroscopic tumors were detected. Analysis of the glucose metabolism did not show clear differences that would explain the increased mortality. Glucose supplementation, either systemically or directly into the brain, did not enhance DKO survival. Lipidic liver metabolism was altered as there was a delay in the activation of genes related to \u03b2-oxidation and a decrease in lipogenesis in DKO mice. High-fat diet administration in DKO significantly improved its life span. Lack of vitamin D signaling increases mortality in a model of overactivation of the IR by impairing lipid metabolism. Clinically, these results reveal the importance of adequate Vitamin D levels in T1D patients.<\/jats:p>","DOI":"10.3390\/nu14071516","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T11:26:07Z","timestamp":1649157967000},"page":"1516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism"],"prefix":"10.3390","volume":"14","author":[{"given":"Maria","family":"Crespo-Masip","sequence":"first","affiliation":[{"name":"Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida, Dr. Pifarr\u00e9 Foundation (IRBLleida), 25198 Lleida, Spain"},{"name":"Medicine Department, University of Lleida, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3456-6902","authenticated-orcid":false,"given":"Aurora","family":"Perez-Gomez","sequence":"additional","affiliation":[{"name":"Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida, Dr. Pifarr\u00e9 Foundation (IRBLleida), 25198 Lleida, Spain"},{"name":"Medicine Department, University of Lleida, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Garcia-Carrasco","sequence":"additional","affiliation":[{"name":"Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida, Dr. Pifarr\u00e9 Foundation (IRBLleida), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4914-5804","authenticated-orcid":false,"given":"Ramiro","family":"Jover","sequence":"additional","affiliation":[{"name":"Experimental Hepatology Unit, IIS Hospital La Fe, 46026 Valencia, Spain"},{"name":"Research Network Center for Liver and Digestive Diseases (CIBERehd), 28029 Madrid, Spain"},{"name":"Biochemistry and Molecular Biology Department, University of Valencia, 46100 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Experimental Hepatology Unit, IIS Hospital La Fe, 46026 Valencia, Spain"},{"name":"Research Network Center for Liver and Digestive Diseases (CIBERehd), 28029 Madrid, Spain"},{"name":"Biochemistry and Molecular Biology Department, University of Valencia, 46100 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-0449","authenticated-orcid":false,"given":"Xavier","family":"Dolcet","sequence":"additional","affiliation":[{"name":"Oncological Pathology Research Group, IRBLleida, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0590-946X","authenticated-orcid":false,"given":"Merc\u00e9","family":"Ibarz","sequence":"additional","affiliation":[{"name":"Indicators and Specifications of the Quality in the Clinical Laboratory Group, IRBLleida, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida, Dr. Pifarr\u00e9 Foundation (IRBLleida), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4746-8538","authenticated-orcid":false,"given":"\u00c0uria","family":"Eritja","sequence":"additional","affiliation":[{"name":"Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida, Dr. Pifarr\u00e9 Foundation (IRBLleida), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Miguel","family":"Diaz-Tocados","sequence":"additional","affiliation":[{"name":"Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida, Dr. Pifarr\u00e9 Foundation (IRBLleida), 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1343-0184","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Valdivielso","sequence":"additional","affiliation":[{"name":"Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida, Dr. Pifarr\u00e9 Foundation (IRBLleida), 25198 Lleida, Spain"},{"name":"Medicine Department, University of Lleida, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1056\/NEJM199309303291401","article-title":"The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus","volume":"329","author":"Nathan","year":"1993","journal-title":"N. 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