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PRMT1 promotes glucose toxicity-induced β cell dysfunction by regulating the nucleo-cytoplasmic trafficking of PDX-1 in a FOXO1-dependent manner in INS-1 cells

Overview of attention for article published in Endocrine, February 2015
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Title
PRMT1 promotes glucose toxicity-induced β cell dysfunction by regulating the nucleo-cytoplasmic trafficking of PDX-1 in a FOXO1-dependent manner in INS-1 cells
Published in
Endocrine, February 2015
DOI 10.1007/s12020-015-0543-8
Pubmed ID
Authors

Lixia Lv, Hewen Chen, Jiaying Sun, Di Lu, Chen, Dongfang Liu

Abstract

Protein N-arginine methyltransferase-1 (PRMT1), the major asymmetric arginine methyltransferase, plays important roles in various cellular processes. Previous reports have demonstrated that levels and activities of PRMT1 can vary in animals with type 2 diabetes mellitus. The aim of this study was to assess the expression and mechanism of action of PRMT1 during glucose toxicity-induced β cell dysfunction. Liposome-mediated gene transfection was used to transfect INS-1 cells with siPRMT1, which inhibits PRMT1 expression, and pALTER-FOXO1, which overexpresses forkhead box protein O1 (FOXO1). The cells were then cultured in media containing 5.6 or 25 mmol/L glucose with or without the small molecule PRMT1 inhibitor AMI-1 for 48 h. The protein levels of PRMT1, the arginine methylated protein α-metR, FOXO1, Phospho-FOXO1, pancreas duodenum homeobox-1 (PDX-1), and the intracellular localization of PDX-1 and FOXO1 were then measured by western blotting. FOXO1 methylation was detected by immunoprecipitated with anti-PRMT1 antibody and were immunoblotted with α-metR. The levels of insulin mRNA were measured by real-time fluorescence quantitative PCR. Glucose-stimulated insulin secretion (GSIS) and intracellular insulin content were measured using radioimmunoassays. Intracellular Ca(2+) ([Ca(2+)]i) was detected using Fura-2 AM. Intracellular cAMP levels were measured using ELISA. Chronic exposure to high glucose impaired insulin secretion, decreased insulin mRNA levels and insulin content, increased intracellular [Ca(2+)]i and cAMP levels, and abolishes their responses to glucose. Inhibiting PRMT1 expression improved insulin secretion, increased mRNA levels and insulin content by regulating the intracellular translocation of PDX-1 and FOXO1, decreasing the methylation of FOXO1, and reducing intracellular [Ca(2+)]i and cAMP concentrations. Transient overexpression of constitutively active FOXO1 in nuclear reversed the AMI-1-induced improvement of β cell function without changing arginine methylation. It is concluded therefore that PRMT1 regulates GSIS in INS-1 cells, through enhanced methylation-induced nuclear localization of FOXO1, which subsequently suppresses the nuclear localization of PDX-1. Our results suggest a novel mechanism that might contribute to the deficient insulin secretion observed under conditions of chronically hyperglycemia.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 3%
Unknown 29 97%

Demographic breakdown

Readers by professional status Count As %
Student > Master 9 30%
Student > Bachelor 3 10%
Student > Postgraduate 3 10%
Student > Ph. D. Student 3 10%
Researcher 2 7%
Other 6 20%
Unknown 4 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 53%
Medicine and Dentistry 4 13%
Agricultural and Biological Sciences 2 7%
Nursing and Health Professions 1 3%
Psychology 1 3%
Other 1 3%
Unknown 5 17%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 February 2015.
All research outputs
#20,258,256
of 22,787,797 outputs
Outputs from Endocrine
#1,359
of 1,681 outputs
Outputs of similar age
#300,857
of 357,412 outputs
Outputs of similar age from Endocrine
#26
of 35 outputs
Altmetric has tracked 22,787,797 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,681 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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