A Light Activated Glucagon Trimer with Resistance to Fibrillation

In this work, we have brought the release of glucagon under the control of light. The aim of this approach is to allow minimally invasive, two-hormone control of blood glucose. Glucagon has two major challenges associated with its therapeutic application: (1) the required amount and timing of glucagon release is highly variable, and (2) glucagon rapidly fibrillates in solution, forming aggregates that are inactive. We have developed a light activated glucagon trimer, in which we have joined three glucagon molecules via light cleaved linkers. We demonstrated that this material can be stimulated by light to release glucagon in a predictable manner. In addition, we demonstrated that in the absence of light, the trimer does not form fibrils and thus releases normal unfibrillated glucagon upon irradiation. These qualities make this material ideal for incorporation into a two hormone light-activated artificial pancreas system.