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Published on: September 9, 2021
Sox17 regulates insulin secretion in the normal and pathologic mouse β cell
Diva Jonatan1, Jason R Spence2, Anna M Method1
1Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
SOX17 regulates insulin secretion and trafficking. Its deletion causes prediabetes and diabetes susceptibility, while its overexpression corrects defects, suggesting therapeutic potential for diabetes.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- SOX17 is a transcriptional regulator influencing beta cell function.
- Its role in pancreatic development and insulin secretion is not fully understood.
Purpose of the Study:
- To investigate the role of SOX17 in pancreatic development and insulin secretion.
- To explore SOX17's potential as a therapeutic target for diabetes.
Main Methods:
- Generated pancreas-specific Sox17 knockout (Sox17-paLOF) mice.
- Utilized Ins2-rtTA driver mice for Sox17 overexpression studies.
- Analyzed insulin secretion, proinsulin trafficking, and transcriptional changes.
Main Results:
- Sox17 deletion did not affect pancreas development but led to prediabetic phenotypes.
- Sox17-paLOF mice showed impaired proinsulin trafficking and increased diabetes susceptibility.
- SOX17 overexpression enhanced insulin secretion and reversed defects in MODY4 models.
Conclusions:
- SOX17 plays a critical role in regulating insulin trafficking and secretion.
- Modulating SOX17 pathways offers a potential therapeutic strategy for diabetes treatment.
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