A Light Activated Glucagon Trimer with Resistance to Fibrillation

Area of Science:

• Biotechnology
• Biomedical Engineering
• Endocrinology

Background:

• Therapeutic glucagon administration faces challenges with variable release timing and rapid fibrillation into inactive aggregates.
• Current methods for managing blood glucose, particularly in artificial pancreas systems, require precise hormone delivery.

Purpose of the Study:

• To develop a light-inducible system for controlled glucagon release.
• To engineer a stable glucagon formulation that prevents fibrillation.
• To create a component for a minimally invasive, two-hormone artificial pancreas.

Main Methods:

• A glucagon trimer was synthesized by linking three glucagon molecules using light-cleavable linkers.
• The light-activated glucagon trimer's release kinetics were evaluated upon light stimulation.
• The stability of the trimer in solution without light and its fibrillation properties were assessed.

Main Results:

• The light-activated glucagon trimer demonstrated predictable glucagon release upon controlled light exposure.
• In the absence of light, the trimer remained stable and did not form fibrils.
• Irradiation with light resulted in the release of unfibrillated, active glucagon.

Conclusions:

• The developed light-activated glucagon trimer offers a controllable and stable method for glucagon delivery.
• This system addresses key challenges in therapeutic glucagon use, particularly fibrillation.
• The engineered glucagon trimer is a promising candidate for integration into light-activated artificial pancreas technologies for improved blood glucose regulation.