The majority of the long-acting insulin analogs undergo rapid degradation after subcutaneous administration, leading to derivatives that differ only slightly from the parent molecules. Typically, only 1-3 terminal basic amino acids located at the terminus of chain B are deleted. Bearing in mind that most insulin analogs are substances that differ from human insulin in a comparable degree and still have distinct biological properties, one may suspect that modifications of analogs molecules, occurring in body fluids as a result of their interaction with degradative enzymes naturally present in the body, could probably lead to derivatives with altered characteristics as well.
The main purpose of the project presented on the poster was to explain to what extent the biological properties of metabolites of innovative insulin analogs differ from the properties of both - the parent molecules and human insulin (used here as the reference). It was also important to verify if the new molecules formed after analogs’ contact with body fluids are safe for diabetic patients. Having a deeper understanding of the mechanisms of the cell state control through the interaction of insulin receptor with molecules that are very similar to each other not only allows to select the analog of the most interesting properties from the set of innovative drug candidtaes being tested, but also facilitates the targeted design of new particles for the treatment of diabetes in the future.
The poster contains a summary of the experiments examining the degree of insulin receptor phosphorylation and activation of major metabolic pathways as a result of the interaction of the tested substances with the cells of selected cell lines.