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Updated: May 10, 2026

Isolated Pancreatic Islet Treatment and Apoptosis Measurement
Published on: May 2, 2025
Blockage of progesterone receptor effectively protects pancreatic islet beta cell viability
Rong Zhou1, Xingang Yao, Xing Xu
1School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Abstract:
The progesterone receptor (PR), a member of nuclear receptor superfamily, is closely associated with gestational, type 1 and type 2 diabetes. However, the underlying mechanisms remain obscure. Here we found that PR activation increased the pro-inflammatory cytokines (PIC)-induced injury in Min6 cells, and PR blockage with siRNA interference protected the cells from damage. Moreover, the new discovered PR antagonist SC51089 effectively improved cell survival by reducing the PIC-stimulated cell apoptosis in Min6 cells. Immunoblotting assays indicated that either PR agonist progesterone (P4) or PR-B over-expression promoted the PIC-induced reinforces of extracellular-signal-regulated kinase 1/2 phosphorylation (p-Erk) and protein 53 (p53), and the attenuations of protein kinase B phosphorylation (p-AKT) and tumor necrosis factor receptor-associated factor 2 (TRAF2). SC51089 could reverse all the P4- or PR-B over-expression induced effects. In addition, PR siRNA inference based assay further supported that SC51089 protected pancreatic islet beta cells from the PR activation or PIC-induced injury by targeting PR and this protective action was mediated by AKT signaling pathway. To our knowledge, this current work might be the first report on the regulation of PR in pancreatic islet beta cell survival. It is expected that SC51089, as a non-steroid PR antagonist, might also find its potential in anti-diabetic research.
Insights
Progesterone receptor (PR) activation worsens inflammation-induced pancreatic cell injury, but the antagonist SC51089 protects these cells. This finding offers potential for new anti-diabetic therapies targeting PR signaling.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- The progesterone receptor (PR) is implicated in diabetes, but its role in pancreatic islet beta cell survival is unclear.
- Understanding PR's mechanism in beta cells is crucial for developing diabetes treatments.
Purpose of the Study:
- To investigate the role of PR in pro-inflammatory cytokine (PIC)-induced pancreatic islet beta cell injury.
- To evaluate the protective effects of the PR antagonist SC51089 on beta cells.
Main Methods:
- Utilized Min6 pancreatic beta cell line.
- Employed siRNA interference for PR knockdown.
- Administered PR agonist progesterone (P4) and antagonist SC51089.
- Performed immunoblotting to assess protein phosphorylation (p-Erk, p-AKT) and expression (p53, TRAF2).
Main Results:
- PR activation exacerbated PIC-induced beta cell injury.
- PR blockage with siRNA or SC51089 protected cells from apoptosis.
- SC51089 reversed P4 or PR-B overexpression-induced changes in Erk, AKT, p53, and TRAF2 signaling.
- SC51089's protective effect was mediated by the AKT signaling pathway.
Conclusions:
- PR plays a significant role in regulating pancreatic islet beta cell survival.
- The PR antagonist SC51089 demonstrates potential therapeutic value in protecting beta cells from inflammatory damage.
- SC51089 may represent a novel non-steroid therapeutic agent for anti-diabetic research.
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