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| Status |
Public on Jul 28, 2020 |
| Title |
Identification of an Anti-diabetic, Orally Available Small Molecule that Regulates TXNIP Expression and Glucagon Action |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Diabetes is characterized by hyperglycemia, loss of functional islet beta cell mass, deficiency of glucose-lowering insulin, and persistent alpha cell secretion of gluconeogenic glucagon. Still, no therapies that target these underlying processes are available. We therefore performed high-throughput screening of 300,000 compounds and extensive medicinal chemistry optimization and here report the discovery of SRI-37330, an orally bioavailable, non-toxic small molecule, which effectively rescued mice from streptozotocin- and obesity-induced (db/db) diabetes. Interestingly, in rat cells and in mouse and human islets, SRI-37330 inhibited expression and signaling of thioredoxin-interacting protein, which we have previously found to be elevated in diabetes and to have detrimental effects on islet function. In addition, SRI-37330 treatment inhibited glucagon secretion and function, reduced hepatic glucose production, and reversed hepatic steatosis. Thus, these studies describe a newly designed chemical compound that, compared to currently available therapies, may provide a distinct and effective approach to treating diabetes.
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| Overall design |
High-throughput screening of 300,000 compounds and extensive medicinal chemistry optimization.
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| Contributor(s) |
Shalev A, Sethupathy P, Kanke M |
| Citation(s) |
32726606 |
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| Submission date |
Jun 01, 2020 |
| Last update date |
Oct 27, 2020 |
| Contact name |
Praveen Sethupathy |
| Organization name |
Cornell University
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| Lab |
Dr. Sethupathy Lab
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| Street address |
Cornell University College of Veterinary Medicine, Box 17
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| City |
Ithica |
| State/province |
NY |
| ZIP/Postal code |
14853 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA636404 |
| SRA |
SRP265520 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE151588_DESeq_normalized_counts_TXNIPinhib.csv.gz |
1.3 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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