C-peptide, a biological molecule co-released with active insulin from the pancreas, is of emerging interest for its beneficial hormonal-like activities. Initially thought to be inert, it is now well-accepted that C-peptide demonstrates therapeutic promise in ameliorating diabetes-related disorders such as kidney dysfunction and vascular neuropathies. However, the molecular mechanisms behind the peptide remain unclear. Understanding how the components that make up the bloodstream influences C-peptide structure and stability is necessary to build a better foundation of how the peptide elicits its beneficial effects. Our previous work has shown that micronutrient metals, such as copper, can directly bind to C-peptide and alter its cellular internalization. Because metal ions can influence C-peptide’s mode of action, the next step is to determine how copper/C-peptide structure can influence peptide stability. Serum albumin is one of the most abundant serum protein chaperones in the bloodstream and is a major constituent for exchangeable copper pool in blood plasma. Because of this, ternary complexation may form between C-peptide, serum albumin, and copper. To determine the role serum albumin and copper may have on C-peptide's activity, various spectroscopic techniques such as CD, UV-Vis, and Trp fluorescence were used, as well as immunofluorescence. Direct changes in peptide binding and cellular internalization displayed a specific ternary schematic between C-peptide, serum albumin, and copper. Overall, serum albumin could be the key to a better understanding of how the peptide induces its physiological effects, which can aid in effective C-peptide formulation.

Investigating the role of copper in mediating interactions between proinsulin C-peptide and serum albumin

ACS Fall 2021

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