Enhanced glucose regulation potential of C-peptide mimics†

The connecting peptide (C-peptide), once relegated as an epiphenomenon in insulin biosynthesis, has now been recognized for its capacity to instigate molecular effects along with important physiological functions. These findings suggest that C-peptide is a hormonally active molecule responsible for controlling a number of diabetes-related complications, in addition to proinsulin processing. Notably, it demonstrates cellular responsiveness and acts as a robust biomarker for beta cell functions, with a half-life longer than that of insulin. Herein, we investigated the effect of some synthetic C-peptide mimics on glucose homeostasis, specifically focusing on glucose uptake, GLUT4 translocation and associated membrane trafficking processes. The glucose utilization potential of some of the C-peptide mimics in L6 muscle myotubes was significantly better than that of the human C-peptide. One of the synthesized C-peptide mimics, CP8, showed glucose metabolism akin to insulin, including potential for Akt phosphorylation and IRβ autophosphorylation. Also, it showed the ability to mitigate intramolecular reactive oxygen species production. The results obtained here highlight the potential of C-peptide mimics on glucose metabolism, as well as interaction with Akt and IRβ, positioning them as promising candidates for future diabetes research.