RSPO1, a potent inducer of pancreatic β cell neogenesis
Serena Silvano1, Tiziana Napolitano1, Magali Plaisant1
1DiogenX, 180 Avenue du Prado, 13008 Marseille, France.
Abstract:
Inducing the neogenesis of pancreatic insulin-producing β cells holds great promise for diabetes research. However, non-toxic compounds with such activities remain to be discovered. Herein, we report the identification of RSPO1, a key agonist of the Wnt/β-catenin pathway, as an inducer of β cell replication. Specifically, we provide evidence that RSPO1 promotes a significant increase in β cell neogenesis in vitro, ex vivo, and in vivo. Importantly, RSPO1 administration is sufficient to activate Wnt/β-catenin signaling in β cells and counter chemically induced or autoimmune-mediated diabetes. Similarly, an optimized analog of RSPO1, allowing for weekly administration, also prevents diabetes in vivo. Lastly, the treatment of transplanted human islets with RSPO1 induces a significant 2.78-fold increase in human β cell numbers in only 60 days, these cells being functional. Such activities of RSPO1 to promote β cell neogenesis could therefore represent an unprecedented hope in the continued search for diabetes alternative therapies.
Insights
Researchers discovered RSPO1, a Wnt/β-catenin pathway agonist, can induce pancreatic beta cell replication. This finding offers new hope for diabetes treatment by promoting beta cell neogenesis.
Area of Science:
- Endocrinology
- Regenerative Medicine
- Molecular Biology
Background:
- Pancreatic beta cell neogenesis is a promising area for diabetes research.
- Discovery of non-toxic compounds that induce beta cell regeneration is crucial.
- The Wnt/β-catenin pathway plays a role in cell growth and development.
Purpose of the Study:
- To identify novel compounds that can induce pancreatic beta cell neogenesis.
- To investigate the potential of RSPO1 as a therapeutic agent for diabetes.
Main Methods:
- In vitro, ex vivo, and in vivo studies were conducted.
- RSPO1's effect on Wnt/β-catenin signaling in beta cells was assessed.
- Chemically induced and autoimmune diabetes models were used.
- Treatment of transplanted human islets with RSPO1 was performed.
Main Results:
- RSPO1 significantly increased beta cell neogenesis across all tested models.
- RSPO1 activated Wnt/β-catenin signaling in beta cells.
- RSPO1 administration prevented chemically induced and autoimmune diabetes.
- An optimized RSPO1 analog enabled weekly administration and diabetes prevention.
- RSPO1 treatment of human islets resulted in a 2.78-fold increase in functional beta cells within 60 days.
Conclusions:
- RSPO1 is a potent inducer of pancreatic beta cell neogenesis.
- RSPO1 demonstrates therapeutic potential for treating diabetes by promoting beta cell regeneration.
- These findings offer a novel therapeutic strategy for diabetes alternative therapies.
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