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母体维生素D限制饮食会对成年小鼠后代的胰岛/胰岛素信号形成产生影响。

Maternal vitamin D-restricted diet has consequences in the formation of pancreatic islet/insulin-signaling in the adult offspring of mice.

作者信息

Maia-Ceciliano Thais C, Barreto-Vianna Andre R C, Barbosa-da-Silva Sandra, Aguila Marcia B, Faria Tatiane S, Mandarim-de-Lacerda Carlos A

机构信息

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.

出版信息

Endocrine. 2016 Oct;54(1):60-69. doi: 10.1007/s12020-016-0973-y. Epub 2016 May 3.

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.

摘要

母体维生素D缺乏可影响小鼠子代的器官发生,是成年后患慢性疾病的一个危险因素。本研究调查母体维生素D缺乏对后代胰岛结构重塑和胰岛素信号通路的影响。我们研究了3月龄雄性C57Bl/6子代(每组n = 10只),其母鼠喂食两种饮食之一:对照饮食(C)或维生素D限制饮食(VitD)。断奶后,子代随意进食对照饮食。在子代中,我们研究了胰岛素分泌、胰岛重塑以及胰岛素信号通路的胰岛蛋白表达(蛋白质印迹法,分离的胰岛,每组n = 5只)。与C组子代相比,VitD组子代血糖更高(P = 0.012),β细胞量更小(P = 0.014),胰岛素血症更低(P = 0.024)。将VitD组子代与C组子代比较,我们观察到胰岛中胰岛素(P = 0.003)、胰岛素受体底物-1(P = 0.025)、磷脂酰肌醇-3-激酶(P = 0.)、3-磷酸肌醇依赖性蛋白激酶1(P = 0.017)、蛋白激酶B(P = 0.028)的蛋白水平较低,胰腺/十二指肠同源框-1(PDX-1)(P = 0.016)、葡萄糖转运蛋白-2(P = 0.003)和葡萄糖激酶(P = 0.045)的表达降低。母体维生素D限制饮食改变了子代胰腺的发育,导致胰岛重塑和胰岛素信号通路改变。PDX-1的减少可能对成年期β细胞量和胰岛素分泌的变化具有重要意义。

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