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Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism

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Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism

dc.contributor.author	Crespo Masip, María
dc.contributor.author	Pérez Gómez, Aurora
dc.contributor.author	García Carrasco, Alicia
dc.contributor.author	Jover Atienza, Ramiro
dc.contributor.author	Guzmán, Carla
dc.contributor.author	Dolcet, Xavier
dc.contributor.author	Ibarz, Mercé
dc.contributor.author	Martínez, Cristina
dc.contributor.author	Eritja, Àuria
dc.contributor.author	Diaz Tocados, Juan Miguel
dc.contributor.author	Valdivielso, Jose Manuel
dc.date.accessioned	2023-05-29T11:14:38Z
dc.date.available	2023-05-29T11:14:38Z
dc.date.issued	2022
dc.identifier.citation	Crespo Masip, María Pérez Gómez, Aurora García Carrasco, Alicia Jover Atienza, Ramiro Guzmán, Carla Dolcet, Xavier Ibarz, Mercé Martínez, Cristina Eritja, Àuria Diaz Tocados, Juan Miguel Valdivielso, Jose Manuel 2022 Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism Nutrients 14 7 1 16
dc.identifier.uri	https://hdl.handle.net/10550/87059
dc.description.abstract	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 β-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
dc.language.iso	eng
dc.relation.ispartof	Nutrients, 2022, vol. 14, num. 7, p. 1-16
dc.subject	Bioquímica
dc.subject	Biologia
dc.title	Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism
dc.type	journal article
dc.date.updated	2023-05-29T11:14:39Z
dc.identifier.doi	10.3390/nu14071516
dc.identifier.idgrec	159247
dc.rights.accessRights	open access