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
- Factor de Impacto:
- 1,287 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Nutrients MDPI
Documentos
- No hay documentos
Filiaciones
Keywords
- diabetes; fatty acids; hypoglycemia; insulin overdose; lipolysis
Proyectos asociados
DESARROLLO DE UN MODELO HEPATOCELULAR HUMANO DIFERENCIADO PARA ESTUDIOS DE METABOLISMO Y POTENCIAL INDUCTOR DE NUEVOS FARMACOS
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
SAF2003-09353 . 2003
DEVELOPMENT OF A HIGH THROUGHPUT GENOMICS-BASED TEST FOR ASSESSING GENOTOXIC AND CARCINOGENIC PROPERTIES OF CHEMICAL COMPOUNDS IN VITRO
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
CARCINOGENOMICS . COMISION EUROPEA . 2006
LINTOP
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
LSHB-CT-2006-037499 - LINTOP . FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2005
MECANISMOS TRNACRIPCIONALES IMPLICADOS EN LA ETIOLOGIA DEL HIGADO GRASO NO ALCOHOLICO. ESTUDIOS EN UN MODELO CELULAR HUMANO DE ESTEATOSIS Y APLICACION AL TRANSPLANTE DE HEPATOCITOS EN TERAPIA CELULAR.
Investigador Principal: RAMIRO JOVER ATIENZA
PI07/0550 . INSTITUTO DE SALUD CARLOS III . 2007
MECANISMOS TRANSCRIPCIONALES IMPLICADOS EN EL HIGADO GRASO NO ALCOHOLICO DE ORIGEN METABOLICO E IATROGENICO: INFLUENCIA DE LA RESISTENCIA A LA INSULINA
Investigador Principal: RAMIRO JOVER ATIENZA
PI10/00194 . INSTITUTO DE SALUD CARLOS III . 2010
ESTEATOSIS HEPÁTICA POR MEDICAMENTOS: NUEVOS MECANISMOS Y BIOMARCADORES APLICABLES AL DESARROLLO FARMACÉUTICO Y A UNA TERAPIA MÁS RACIONAL EN PACIENTES CON SÍNDROME METABÓLICO.
Investigador Principal: RAMIRO JOVER ATIENZA
PI13/01470 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2014
Nuevos mecanismos y biomarcadores diagnósticos en la colestasis iatrogénica.
Investigador Principal: RAMIRO JOVER ATIENZA
PI17/01089 . INSTITUTO DE SALUD CARLOS III . 2018
Susceptibility factors and non-invasive biomarkers for liver steatosis induced by valproate in pediatric epileptic patients.
Investigador Principal: RAMIRO JOVER ATIENZA
PI20/00690 . INSTITUTO DE SALUD CARLOS III . 2021
Cita
Crespo M,Perez A,Garcia A,Jover R,Guzman C,Dolcet X,Ibarz M,Martinez 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).