The influence of amylin on the bile acid spectrum in rats

Ip, Vasheka; Sp, Vesel'skyĭ; Za, Horenko; Oa, Hrinchenko; Ls, Karbovs'ka; MIu, Makarchuk

doi:10.15407/fz60.03.046

Cited by 5 publications

(2 citation statements)

References 30 publications

(33 reference statements)

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“…Currently, the role of IAPP in cholesterol metabolism has not been elucidated. For instance, one study conducted in rats, which subcutaneous administration of IAPP changes the proportion of trihydroxy and dihydroxycholates in the secretion of bile, improving the processes of conjugation and hydroxylation in hepatocytes ( 50 ). In addition, although it has been reported that pramlintide treatment reduced circulating triglycerides in DM2 patients, significant differences in blood pressure, HDL, and LDL cholesterol has not been found ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Amyloidogenesis Controlled by the C-Terminal Domain of Islet Amyloid Polypeptide Shows New Functions on Hepatocyte Cholesterol Metabolism

et al. 2018

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The islet amyloid polypeptide (IAPP) or amylin maintains a key role in metabolism. This 37-residues-peptide could form pancreatic amyloids, which are a characteristic feature of diabetes mellitus type 2. However, some species do not form amyloid fibril structures. By employing a biomimetic approach, we generated an extensive panel of optimized sequences of IAPP, which could drastically reduce aggregation propensity. A structural and cellular characterization analysis was performed on the C-terminal domain with the highest aggregation propensity. This allowed the observation of an aggregative phenomenon dependent of the lipid environment. Evaluation of the new F23R variant demonstrated inhibition of β-sheet structure and, therefore, amyloid formation on the native C-terminal, phenomenon that was associated with functional optimization in calcium and cholesterol management coupled with the optimization of insulin secretion by beta cells. When F23R variant was evaluated in microglia cells, a model of amyloidosis, cytotoxic conditions were not registered. In addition, it was found that C-terminal sequences of IAPP could modulate cholesterol metabolism in hepatocytes through regulation of SREBP-2, apoA-1, ABCA1, and LDLR, mechanism that may represent a new function of IAPP on the metabolism of cholesterol, increasing the LDL endocytosis in hepatocytes. Optimized sequences with only one residue modification in the C-terminal core aggregation could diminish β-sheet formation and represent a novel strategy adaptable to other pharmacological targets. Our data suggest a new IAPP function associated with rearrangements on metabolism of cholesterol in hepatocytes.

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Section: Discussionmentioning

confidence: 99%

Modulation of Amyloidogenesis Controlled by the C-Terminal Domain of Islet Amyloid Polypeptide Shows New Functions on Hepatocyte Cholesterol Metabolism

et al. 2018

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“…Отже, наші результати можуть свідчити про пригнічення активності транспортерів таури-ну та зменшення надходження цієї амінокис-лоти до гепатоцитів на 13-ту добу перебігу хронічного панкреатиту. Важливе значення для оцінки функціо-нального стану печінки та якості секре-тованої жовчі є співвідношення окремих груп жовчних кислот [31]. Співвідношення кон'югованих і вільних холатів -один з по-казників детоксикаційної, а тригідрокси-та дигідроксихоланових -синтетичної функцій печінки.…”

Section: результати та їх обговоренняunclassified