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Series GSE181328 Query DataSets for GSE181328
Status Public on Dec 03, 2021
Title Omics Reveal Far Reaching Effects of Verapamil Treatment in Subjects with Type 1 Diabetes
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Currently, no oral medications are available for individuals suffering from type 1 diabetes (T1D). Our randomized placebo-controlled phase 2 trial recently revealed that oral verapamil has short- term beneficial effects in subjects with new-onset type 1 diabetes (T1D) 1. However, what exact biological changes verapamil elicits in humans with T1D, how long they may last, and how to best monitor any associated therapeutic success has remained elusive. We therefore now conducted extended analyses of the effects of continuous verapamil use over a 2-year period, performed unbiased proteomics analysis of serum samples and assessed changes in proinflammatory T-cell markers in subjects receiving verapamil or just standard insulin therapy. In addition, we determined the verapamil-induced changes in human islets using RNA sequencing. Our present results reveal that verapamil regulates the thioredoxin system and promotes an anti-oxidative and anti-apoptotic gene expression profile in human islets, reverses T1D-induced elevations in circulating proinflammatory T-follicular-helper cells and interleukin-21 and normalizes serum levels of chromogranin A (CHGA), a recently identified T1D autoantigen 2,3. In fact, proteomics identified CHGA as the top serum protein altered by verapamil and as a potential therapeutic marker. Moreover, continuous use of oral verapamil delayed T1D progression, promoted endogenous beta cell function and lowered insulin requirements and serum CHGA levels for at least 2 years and these benefits were lost upon discontinuation. Thus, the current studies provide crucial mechanistic and clinical insight into the beneficial effects of verapamil in T1D.
 
Overall design Treatment of islet cells with compond (verapamil) followed by transcriptomics.
 
Contributor(s) Shalev A, Sethupathy P, Kanke M
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Submission date Aug 02, 2021
Last update date Dec 03, 2021
Contact name Praveen Sethupathy
Organization name Cornell University
Lab Dr. Sethupathy Lab
Street address Cornell University College of Veterinary Medicine, Box 17
City Ithica
State/province NY
ZIP/Postal code 14853
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (6)
GSM5494795 Control_1
GSM5494796 Control_2
GSM5494797 Control_3
Relations
BioProject PRJNA751582
SRA SRP330881

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Supplementary file Size Download File type/resource
GSE181328_DESeq_normalized_counts.csv.gz 1.3 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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