Beta cell failure is the central cause of type-2 diabetes. Researchers at UCI have developed molecules for treating diabetes that target proteins on the surface of beta cells and induce their clustering. This clustering results in an increase in insulin secretion and content and promotion of beta cell maturation. Furthermore, the clustering effect seen with these compositions may promote both proliferation and the reversal of de-differentiation.
Inventors at UCI have identified specific proteins on the surface of pancreatic beta cells that, when bound with proteins on the surface of adjacent cells in a clustered fashion, can promote beta cell maturation, increase beta cell function, increase insulin secretion, and provide resistance to stressors. Targeting these proteins, the inventors have developed molecules, including peptide mimetics and full-length proteins, which mimic these proteins, allowing for binding in a clustered fashion. These molecules can be applied to pancreatic beta cells to restore insulin secretion and protect the cells from further stress.
In the figure below, insulin secretion is measured comparing one of the molecules, HAS-28P to other control treatments in mouse islets.
Investigators are currently testing the effect of these molecules on precursor cells and stem cells to promote proper maturation and differentiation. Nanoparticle formulations have been tested to enhance delivery of the molecules.
Future Development Plans
Researchers plan in vivo and further in vitro testing in the near future. In vivo testing will include rodent models for treatment of type 2 diabetes. In vitro testing will focus on efficacy in driving the functional maturation of stem-cell derived beta cell precursors and enhancing glucose-stimulated insulin secretion.