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The role of amino acids from the C-terminus of the insulin B chain in the selectivity towards insulin receptor isoforms.
Polák, Marek ; Žáková, Lenka (advisor) ; Obšilová, Veronika (referee)
The main function of insulin as a hormone is to control glucose homeostasis in the blood. This control takes place at different levels in different parts of the body. The complexity of the regulation of blood glucose levels is manifested through the insulin receptor (IR) and its two isoforms, IR-A and IR-B. IR-B is responsible for metabolic effects and the distribution in adipocytes, muscles and hepatic cells, whereas IR-A has, above all, mitogenic effects with lymphocytes, spleen, brain and cancer cells. Today's treatment of diabetes patients is focused on the use of insulin analogues, insulin replacemensts with a different IR-A and IR-B binding affinity. Today's patients use two different types of analogues, called fast-acting and basal, with a focus on the combination of these two types throughout the day. In 2011, prof. Belfiore from the Universtiry of Catanzzaro published a scientific article about the close relation between diabetes and some cancer types. This article triggered extensive debates about the impact of insulin or insulin analogues on the mitogenic isoform IR-A of the insulin receptor, and IR-A isoform on the insulin-like growth factor type 1. In the same year, two scientific groups from a Danish company Novo Nordisk, published the first hints at receptor isoform-selective insulin...
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