title: Adverse effects of vitamin D deficiency on the Pi3k/Akt pathway and pancreatic islet morphology in diet-induced obese mice.
abstract: METHODS
  To investigate the impact of vitamin D deficiency on insulin resistance and abnormal glucose homeostasis in obesity.
  
  
  RESULTS
  Sixty male C57BL/6 mice (3 months old) were fed a control diet (C-10% energy as fat) or a high-fat diet (HF-50% energy as fat), with or without vitamin D, for 8 weeks. There was no difference in body mass between the HF and HF/VitD- groups. Vitamin D deficiency (VitD) in the diet-induced obese mice increased hyperinsulinemia (p = 0.04), hyperleptinemia (p = 0.0002), insulin resistance (HOMA-IR, p = 0.04), and islet changes, including alpha and beta cell disarray. In the insulin signaling pathway, insulin receptor substrate 2 expression was upregulated in the C/VitD- group (p = 0.001) and downregulated in the HF/VitD- group (p = 0.009). Interestingly, forkhead box protein O1 expression was higher in the HF/VitD- group than in the HF group (p = 0.03), and pancreatic and duodenal homeobox 1 expression was lower in the HF/VitD-group than in the HF group (p = 0.025), indicating that the HF diet and vitamin D deficiency influenced the downregulation of the expression of these proteins (two-way ANOVA, p < 0.0001).
  
  
  CONCLUSIONS
  Vitamin D deficiency exacerbated the adverse structural and physiological remodeling of pancreatic islets due to obesity, contributing to abnormal glucose homeostasis.
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Celina Carvalho
authors.initials: CC
authors.lastname: Borges
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Andreza Fernandes
authors.initials: AF
authors.lastname: Salles
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Isabele
authors.initials: I
authors.lastname: Bringhenti
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Souza-Mello
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcia Barbosa
authors.initials: MB
authors.lastname: Aguila
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001835:Body Weight; D050260:Carbohydrate Metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D020738:Leptin / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014808:Vitamin D Deficiency / Q000150:complications / Q000378:metabolism* / Q000473:pathology*
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D007328:Insulin; D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Insulin resistance; Obesity; Pancreatic islet; Vitamin D deficiency