In utero exposure to phenanthrene induced islet cell dysfunction in adult mice: Sex differences in the effects and potential causes.

Sci Total Environ

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, PR China. Electronic address:

Published: May 2021

Epidemiological studies show that the burden of polycyclic aromatic hydrocarbons in human body is associated with the occurrence of insulin resistance and diabetes. In the present study, pregnant mice were exposed to phenanthrene (Phe) at doses of 0, 60 and 600 μg/kg body weight of by gavage once every 3 days. The female F1 mice at 120 days of age showed no change in their fasting glucose levels (FGLs) but exhibited significantly decreased homeostasis model assessment (HOMA) β-cell (49% and 43%) and significantly downregulated pancreatic proinsulin gene (ins2) transcription. The downregulation of transcription factors, such as PDX1, PAX4 and FGF21, indicated impaired development and function of β-cells. The significantly reduced α-cell mass in 60 and 600 μg/kg groups, and the significantly downregulated expression of proglucagon gene gcg and ARX in the 600 μg/kg group suggested that the development and function of α-cells had been impacted. The males exhibited significantly increased FGLs (1.14- and 1.15-fold) in Phe exposed treatments and significantly elevated HOMA β-cell (3.15-fold) in the 600 μg/kg group. Upregulated ins2 transcription and FGF21 protein in male mice prenatally exposed to 600 μg/kg Phe suggested that these animals appeared compensatory enhancement in β-cell function. The reduced serum estradiol levels and downregulated pancreatic estrogen receptor α and β were responsible for the dysfunction of β-cells in the females. In the males, the significantly elevated androgen levels in the 600 μg/kg group might be related to the upregulated ins2 transcription, and the increased expression of pancreatic FGF21 further demonstrated the enhancement of β-cell potential. The results will be helpful for assessing the risk of developing diabetes in adulthood after prenatal exposure to phenanthrene.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.145295DOI Listing

Publication Analysis

Top Keywords

ins2 transcription
12
600 μg/kg group
12
exposure phenanthrene
8
homa β-cell
8
downregulated pancreatic
8
development function
8
group upregulated
8
upregulated ins2
8
enhancement β-cell
8
600 μg/kg
6

Similar Publications

The immune checkpoint molecule B7-H4 regulates β-cell mass and insulin secretion by modulating cholesterol metabolism through Stat5 signalling.

Mol Metab

November 2024

Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China. Electronic address:

Objective: B7-H4 (B7S1, B7x, VTCN1) is an important immune checkpoint molecule that maintains immune homeostasis and is also expressed in pancreatic β cells. The polymorphism of B7-H4 influences the prevalence of Type 2 diabetes (T2D), suggesting a potential role of B7-H4 in the physiological function of pancreatic β cells and the pathogenesis of T2D.

Methods: β-cell-specific B7-H4 knockout mice (B7-H4 cKO mice) and their wild-type littermates were used to investigate the in vivo effects of B7-H4 on pancreatic β-cell morphology and function.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the roles of BRG1 and BRM ATPase subunits from the SWI/SNF chromatin remodeling complex in the development of endocrine cells, particularly beta cells, which are crucial for insulin production.
  • Researchers created genetically modified mice to analyze the impacts of removing BRG1 in endocrine progenitor cells and varying levels of BRM deficiency, assessing metabolic health and pancreatic islet function.
  • Findings showed that mice with BRG1 and BRM deficiencies faced severe glucose intolerance and reduced insulin secretion due to diminished islet and hormone-producing cell populations, alongside disrupted gene expression crucial for cell differentiation.
View Article and Find Full Text PDF

Purpose: Inflammation is involved in the pathogenesis of diabetes, however the impact of diabetes on organ-specific autoimmune diseases remains unexplored. Experimental autoimmune uveoretinitis (EAU) is a widely accepted animal model of human endogenous uveitis. In this study, we investigated the effects of diabetic conditions on the development of EAU using a mouse diabetes model.

View Article and Find Full Text PDF

Parent-of-origin-specific expression of imprinted genes is critical for successful mammalian growth and development. Insulin, coded by the INS gene, is an important growth factor expressed from the paternal allele in the yolk sac placenta of therian mammals. The tyrosine hydroxylase gene TH encodes an enzyme involved in dopamine synthesis.

View Article and Find Full Text PDF

Missense mutation of ISL1 (E283D) is associated with the development of type 2 diabetes.

Diabetologia

August 2024

Shanghai Diabetes Institute, Department of Endocrinology & Metabolism, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aims/hypothesis: Mutations in Isl1, encoding the insulin enhancer-binding protein islet-1 (ISL1), may contribute to attenuated insulin secretion in type 2 diabetes mellitus. We made an Isl1 mouse model to investigate the disease-causing mechanism of diabetes mellitus.

Methods: The ISL1 mutation (c.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!