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Preparation and characterization of vesiculin, a two-chain protein derived from IGF-2
Mrzílková, Karolína ; Žáková, Lenka (advisor) ; Pačesová, Andrea (referee)
Hormones of insulin family are one of the most studied groups of proteins due to their connection to large number of diseases including type two diabetes mellitus, tumorigenesis and some neurodegenerative diseases. The newest member of this superfamily is a two-chain analogue of IGF-2 called vesiculin. This peptide was originally isolated from secretory granules of mouse βTC6-F7 cell line and is currently believed to have a endocrine or paracrine effect on pancreatic β-cells. Its sequence homology with IGF-2 and structural similarity to insulin foreshadows vesiculin's potential metabolic, proliferation and growth properties and further secures its place as scientifically interesting and clinically lucrative topic. The insulin theme is corelated with insulin resistance, pathological state present primarily in early stages of development of type two diabetes mellitus. Vesiculin is able to stimulate glucose uptake and glycogen synthesis even in this condition which differentiates it form insulin and IGF-2 whose glucoregulatory activity is blunted in face of insulin resistance. Further research of vesiculin and insulin family receptor interaction, including dimeric tyrosinekinase receptor for IGF-1 and insulin, but also monomeric IGF-2 receptor, can provide more knowledge on character of this binding...
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Study of secretory granules from insulin-producing tissues and cell lines.
Halušková, Petra ; Žáková, Lenka (advisor) ; Koblas, Tomáš (referee)
Pancreas is known to be an organ producing a variety of exocrine and endocrine substances, where also insulin belongs. This hormone is produced in the body almost solely by specialized β-cells of the Langerhans islets and is stored here in secretory granules. As the β-cells contain large number of these vesicles, an organism can quickly respond to the glucose stimulation. Completely processed insulin is formed in the secretory granules probably as a hexamer, where six insulin molecules are coordinated along two zinc bivalent cations. Appropriate β-cell response to higher glucose level and following insulin secretion is one of the key processes that regulate metabolism in the body. In order to study insulin production, its effects or secretion, permanent pancreatic cell lines are often used as biological models, out of primary cells from islets of Langerhans. This diploma thesis is focused on two permanent cell lines INS-1E and BRIN-BD11. We searched for the ability of the cells to produce insulin, if the hormone is fully processed, as well as zinc content, which could have a great influence on insulin's processing. Using different methods we compared these two cell lines with cells from the Langerhans islets. We succeeded in isolation of secretory granules from all three cell types and we plan to...
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