SerpinB1 Peptides Stimulate Beta Cell Proliferation
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Solution Overview
Problem
Current therapies for diabetes lack effective methods to promote pancreatic β cell regeneration and increase functional β cell mass, particularly in insulin-resistant states, where known factors do not fully account for β cell proliferation.
Innovation Solution
Identification of SerpinB1 as a hepatocyte-derived factor that stimulates β cell proliferation independently of glucose and insulin levels, using complementary in vivo and in vitro assays, and its application through Serpin peptide or analogs to enhance β cell function and proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If known factors (incretins, adipokines, cytokines, growth factors) are used to promote β cell proliferation, then some β cell growth may occur, but the proliferation is insufficient to fully compensate for insulin resistance
Solution Approach 1:
The patent identifies and utilizes SerpinB1 as an intermediary factor that mediates β cell proliferation. SerpinB1 acts as a specific mediator that bridges the gap between insulin resistance and effective β cell compensation, providing a targeted mechanism that known factors fail to achieve. The patent demonstrates that SerpinB1, when administered, specifically promotes β cell proliferation in insulin-resistant states where other factors have failed.
2Quantity of substance
If β cell mass is increased through self-duplication, then functional β cell mass may improve, but the rate of proliferation is too low to compensate for pathological insulin resistance
Solution Approach 1:
The patent employs parameter changes by introducing SerpinB1 administration to alter the proliferation rate parameter of β cells. This external factor changes the kinetic parameters of β cell division, transforming the slow self-duplication process into an accelerated proliferation response that can effectively compensate for insulin resistance. The patent shows that SerpinB1 treatment significantly increases the proliferation rate compared to untreated controls.
3Quantity of substance
If systemic regulators (incretins, adipokines, myokines, cytokines, growth factors) are utilized, then some β cell growth is promoted, but none fully account for the proliferation observed in insulin-resistant states
Solution Approach 1:
The patent extracts and isolates SerpinB1 as the specific critical factor responsible for β cell proliferation in insulin-resistant states. By separating SerpinB1 from the complex mixture of systemic regulators and identifying it as the key mediator, the patent recovers the missing information about what drives effective β cell compensation. This extraction allows for targeted therapeutic intervention with SerpinB1 alone.
Data Source
AI summary
Compositions and methods of use are provided for improving β cell function and promoting pancreatic β cell proliferation in vitro, in vivo and ex vivo. The active agents of the pending invention comprise Serpin family peptides (e.g., SerpinB1), functional and structural analogs of Serpin family peptides and nucleic acids encoding Serpin family peptides, as well as active fragments thereof.