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Series GSE122566 Query DataSets for GSE122566
Status Public on Nov 16, 2018
Title Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and 2.5ppm iAs Treated Mouse Gastrocnemius Muscle Transcriptomes
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Inorganic arsenic (iAs) is a widespread environmental toxin. In addition to being a human carcinogen, its effect on systemic glucose metabolism has started to gain recognition recently. However, its in vivo effect on insulin sensitivity is not clear. Here we use mouse models to dissect the dose-dependent effects of iAs in glucose metabolism. We found that a low-dose exposure (0.25 ppm iAs in drinking water) caused glucose intolerance in adult male C57BL/6 mice, likely by disrupting glucose-induced insulin secretion without affecting peripheral insulin sensitivity. However, a higher-dose exposure (2.5 ppm iAs) has diminished effects on glucose tolerance despite disrupted pancreatic insulin secretion. We performed hyperinsulinemic euglycemic clamp, the gold standard analysis of systemic insulin sensitivity, and found that the 2.5 ppm iAs enhanced systemic insulin sensitivity by simultaneously enhancing insulin-stimulated glucose uptake in skeletal muscles and insulin-mediated suppression of endogenous glucose production. RNA-seq analysis of muscles revealed that 2.5 ppm iAs regulated expression of many genes involved in the metabolism of fatty acids, pyruvate, and amino acids. These findings suggest that iAs has distinct effects on distinct metabolic tissues at different dose thresholds, which could help reconcile some of the conflicting epidemiological results. The study shed light on the complex interactions between an environmental factor and the systemic glucose metabolism.
Overall design Gastrocnemius Muscle mRNA profiles of 24-week 2.5 ppm iAs in drinking water treatment and control mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 3000.
Contributor(s) Gong Y, Wan Y, Liu J, Sun Z
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Submission date Nov 15, 2018
Last update date Feb 11, 2019
Contact name Jidong Liu
Organization name Baylor College of Medicine
Street address One Baylor Plaza
State/province TX
ZIP/Postal code 77030
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (6)
GSM3473993 ZS.1_4380
GSM3473994 ZS.2_4482
GSM3473995 ZS.3_4505
BioProject PRJNA505628
SRA SRP168746

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Supplementary file Size Download File type/resource
GSE122566_iAs_F0_2.5ppm_Gas_RNAseq.xlsx 4.3 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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