Journal
CELL METABOLISM
Volume 32, Issue 3, Pages 353-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2020.07.002
Keywords
-
Categories
Funding
- NIH [U2CDK093000, U01DK120379, R01DK078752]
- Alabama Drug Discovery Alliance (ADDA)
- NIH Nutrition Obesity Research Center [P30DK056336]
- [UL1TR001417]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available