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子宫内暴露于地塞米松会在出生后早期编程胰腺β-和α-细胞的发育。

In utero exposure to dexamethasone programs the development of the pancreatic β- and α-cells during early postnatal life.

机构信息

Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 105 Alexander Flemming St., Campinas 13083-881, SP, Brazil.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo 05508-000, SP, Brazil.

出版信息

Life Sci. 2020 Aug 15;255:117810. doi: 10.1016/j.lfs.2020.117810. Epub 2020 May 28.

Abstract

AIMS

The aim of the present study was to clarify if in utero exposure to DEX would affect the development of different types of pancreatic endocrine cells during postnatal life.

MAIN METHODS

We investigated morphological and transcriptional features of both pancreatic β- and α-cell populations within the pancreatic islets during the early postnatal life of rats born to mothers treated with DEX (0.1 mg/kg) from day 14 to 19 of pregnancy. Untreated pregnant Wistar rats of the same age (12-week-old) were used as control (CTL). Pups were euthanized on the 1st, 3rd and 21st (PND1, PND3 and PND21, respectively) days of life, regardless of sex. Serum insulin and glucagon levels were also evaluated.

KEY FINDINGS

Rats born to DEX-treated mothers exhibited increased pancreatic α-cell mass, circulating glucagon levels and Gcg, Pax6, MafB and Nkx2.2 expression. Rats born to DEX-treated mothers also presented a rise in serum insulin levels on the PND3 that was paralleled by reduced β-cell mass. Such increase in serum insulin levels, instead, was associated with increased expression of genes associated to insulin secretion such as Gck and Slc2a2.

SIGNIFICANCE

Altogether, the present data reveals yet unknown changes in endocrine pancreas during early postnatal life of rats exposed to DEX in utero. Such data may contribute to the understanding of the metabolic features of rats born to DEX-treated mothers.

摘要

目的

本研究旨在阐明宫内暴露于地塞米松(DEX)是否会影响胎儿在出生后生命期间不同类型的胰腺内分泌细胞的发育。

主要方法

我们研究了来自接受 DEX(0.1mg/kg)治疗的母亲的怀孕 14 至 19 天的大鼠的胰岛内的胰腺β-和α-细胞群体的形态和转录特征。相同年龄(12 周龄)未接受治疗的 Wistar 大鼠用作对照(CTL)。无论性别如何,均在出生后第 1、3 和 21 天(PND1、PND3 和 PND21)处死幼崽。还评估了血清胰岛素和胰高血糖素水平。

主要发现

来自接受 DEX 治疗的母亲的大鼠表现出胰腺α-细胞质量增加、循环胰高血糖素水平和 Gcg、Pax6、MafB 和 Nkx2.2 表达增加。来自接受 DEX 治疗的母亲的大鼠在 PND3 时也表现出血清胰岛素水平升高,这与β-细胞质量减少相平行。这种血清胰岛素水平的增加与与胰岛素分泌相关的基因(如 Gck 和 Slc2a2)的表达增加相关。

意义

总之,本数据揭示了在宫内暴露于 DEX 的大鼠的出生后早期生命中内分泌胰腺的未知变化。这些数据可能有助于理解来自接受 DEX 治疗的母亲的大鼠的代谢特征。

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