Portal de investigación
Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Crespo-Masip, Maria
- Perez-Gomez, Aurora
- Garcia-Carrasco, Alicia
- Guzman, Carla
- Dolcet, Xavier
- Ibarz, Merce
- Martinez, Cristina
- Eritja, Auria
- Miguel Diaz-Tocados, Juan
- Manuel Valdivielso, Jose
Grupos
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 ß-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.
Datos de la publicación
- ISSN/ISSNe:
- 2072-6643, 2072-6643
- Tipo:
- Article
- Páginas:
- -
- DOI:
- 10.3390/nu14071516
- PubMed:
- 35406129
- Enlace a otro recurso:
- www.scopus.com
- Factor de Impacto:
- 1,287 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Nutrients MDPI
Citas Recibidas en Web of Science: 2
Documentos
- No hay documentos
Filiaciones
Keywords
- diabetes; fatty acids; hypoglycemia; insulin overdose; lipolysis
Cita
Crespo M,Perez A,Garcia A,JOVER R,Guzmán C,Dolcet X,Ibarz M,Martínez C,Eritja A,Miguel Diaz J,Manuel J. Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism. Nutrients. 2022. 14. (7):1516. IF:5,900. (1).