Ultrastable Insulin-Glucagon Fusion Protein

The Ultrastable Insulin-Glucagon Fusion Protein is a novel recombinant fusion protein designed to provide glucose-responsive control for diabetes mellitus. It comprises an N-terminal glucagon moiety, stabilized by an α-helix-compatible lactam bridge, and a C-terminal insulin moiety, stabilized as a single chain with a foreshortened C domain. This unique design allows the fusion protein to exploit an endogenous glucose-dependent switch in hepatic physiology, promoting insulin signaling under hyperglycemic conditions and glucagon signaling during hypoglycemia, thereby aiming to mitigate the risk of hypoglycemia while maintaining glycemic control. A key feature of this protein is its enhanced physical stability, exhibiting resistance to fibrillation, which could facilitate easier manufacturing, storage, and global access by potentially circumventing the need for a cold chain. Preclinical studies in rats have demonstrated its proof of concept in regulating blood glucose levels.

Other names

Ultrastable Insulinglucagon-insulin fusion protein