title: Maternal vitamin D-restricted diet has consequences in the formation of pancreatic islet/insulin-signaling in the adult offspring of mice.
abstract: The maternal deficiency of vitamin D can act on organogenesis in mice offspring, being a risk factor for chronic diseases in adulthood. This study investigates the effects of maternal deficiency of vitamin D on structural islet remodeling and insulin-signaling pathway in the offspring. We studied male C57Bl/6 offspring at 3-month old (n = 10/group) from mother fed one of the two diets: control diet (C) or vitamin D-restricted diet (VitD-). After weaning, offspring only fed the control diet ad libitum. In the offspring, we studied insulin production, islet remodeling, and islet protein expression of the insulin-signaling pathway (Western blotting, isolated islet, n = 5/group). VitD-offspring showed greater glycemia (P = 0.012), smaller beta-cell mass (P = 0.014), and hypoinsulinemia (P = 0.024) than C offspring. Comparing VitD-offspring with C offspring, we observed lower protein levels in islet of insulin (P = 0.003), insulin receptor substrate-1 (P = 0.025), phosphatidylinositol-3-kinases (P = 0.045), 3-phosphoinositide-dependent protein kinase 1 (P = 0.017), protein kinase B (P = 0.028), with reduced expression of pancreas/duodenum homeobox-1 (PDX-1) (P = 0.016), glucose transporter-2 (P = 0.003), and glucokinase (P = 0.045). The maternal vitamin D-restricted diet modifies the development of the pancreas of the offspring, leading to islet remodeling and altered insulin-signaling pathway. The decrease of PDX-1 is probably significant to the changes in the beta-cell mass and insulin secretion in adulthood.
authors.affiliation: Laboratorio de Morfometria, Metabolismo e Doenca Cardiovascular, Centro Biomedico, Instituto de Biologia, Universidade do Estado de Rio de Janeiro - UERJ, Av. 28 de Setembro, 87 fds, Rio de Janeiro, RJ, 20551-030, Brazil.
authors.forename: Thais C
authors.initials: TC
authors.lastname: Maia-Ceciliano
authors.affiliation: Laboratorio de Morfometria, Metabolismo e Doenca Cardiovascular, Centro Biomedico, Instituto de Biologia, Universidade do Estado de Rio de Janeiro - UERJ, Av. 28 de Setembro, 87 fds, Rio de Janeiro, RJ, 20551-030, Brazil.
authors.forename: Andre R C
authors.initials: AR
authors.lastname: Barreto-Vianna
authors.affiliation: Laboratorio de Morfometria, Metabolismo e Doenca Cardiovascular, Centro Biomedico, Instituto de Biologia, Universidade do Estado de Rio de Janeiro - UERJ, Av. 28 de Setembro, 87 fds, Rio de Janeiro, RJ, 20551-030, Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Barbosa-da-Silva
authors.affiliation: Laboratorio de Morfometria, Metabolismo e Doenca Cardiovascular, Centro Biomedico, Instituto de Biologia, Universidade do Estado de Rio de Janeiro - UERJ, Av. 28 de Setembro, 87 fds, Rio de Janeiro, RJ, 20551-030, Brazil.
authors.forename: Marcia B
authors.initials: MB
authors.lastname: Aguila
authors.affiliation: Laboratorio de Morfometria, Metabolismo e Doenca Cardiovascular, Centro Biomedico, Instituto de Biologia, Universidade do Estado de Rio de Janeiro - UERJ, Av. 28 de Setembro, 87 fds, Rio de Janeiro, RJ, 20551-030, Brazil.
authors.forename: Tatiane S
authors.initials: TS
authors.lastname: Faria
authors.affiliation: Laboratorio de Morfometria, Metabolismo e Doenca Cardiovascular, Centro Biomedico, Instituto de Biologia, Universidade do Estado de Rio de Janeiro - UERJ, Av. 28 de Setembro, 87 fds, Rio de Janeiro, RJ, 20551-030, Brazil. mandarim@uerj.br.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004032:Diet; D005260:Female; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D015398:Signal Transduction; D014807:Vitamin D / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014807:Vitamin D
keywords: Fetal programming; FoxO1; Insulin pathway; PDX-1; Pancreas