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A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
Published on: July 16, 2016
A multi-parameter, high-content, high-throughput screening platform to identify natural compounds that modulate
Jessica A Hill1, Marta Szabat, Corinne A Hoesli
1Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Plos One
|October 2, 2010
Summary
Researchers screened marine invertebrate extracts to find compounds that regulate pancreatic beta-cell function. This novel approach identified promising compounds for diabetes treatment by modulating insulin and pdx1 gene expression.
Area of Science:
- Endocrinology and Metabolism
- Molecular Biology
- Drug Discovery
Background:
- Diabetes mellitus results from pancreatic beta-cell dysfunction or loss.
- Developing drugs to regenerate or improve beta-cell function is crucial for a diabetes cure.
Purpose of the Study:
- To establish a high-throughput screening platform for identifying compounds that affect beta-cell survival and gene expression.
- To discover novel regulators of insulin and pdx1 gene promoters in pancreatic beta-cells.
Main Methods:
- Utilized a dual-reporter lentivirus system in human islets and MIN6 cells to monitor insulin and pdx1 promoter activity.
- Employed multi-parameter, high-content analysis and B-score statistical transformation for robust screening.
- Screened 1319 marine invertebrate extracts, confirming findings with real-time PCR and radioimmunoassay for insulin secretion.
Main Results:
- Identified 7 marine invertebrate extracts that reproducibly modulated insulin and/or pdx1 promoter activity.
- Confirmed that compounds from these extracts alter insulin mRNA levels and insulin secretion.
- Focused on two lead compounds: one stimulating and one inhibiting insulin gene expression.
Conclusions:
- Multi-parameter, high-content screening effectively identifies novel regulators of beta-cell gene expression.
- This platform is a significant step towards developing new diabetes therapies targeting insulin production.
- Identified compounds like bivittoside D as potential therapeutic agents for diabetes.
