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Коморбідний ендокринологічний пацієнт
Коморбідний ендокринологічний пацієнт

Международный эндокринологический журнал Том 21, №2, 2025

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Епігенетичний вплив довгих некодуючих РНК на розвиток інсулінорезистентності при метаболічно асоційованій жировій хворобі печінки (частина 1)

Епігенетичний вплив довгих некодуючих РНК на розвиток інсулінорезистентності при метаболічно асоційованій жировій хворобі печінки (частина 1)

Авторы: O.E. Abaturov (1), V.S. Berezenko (2, 3), A.O. Nikulina (1)
(1) - Dnipro State Medical University, Dnipro, Ukraine
(2) - Bogomolets National Medical University, Kyiv, Ukraine
(3) - Ukrainian Center of Maternity and Childhood of NAMSU, Kyiv, Ukraine

Рубрики: Эндокринология

Разделы: Справочник специалиста

Версия для печати


Резюме

Інсулінорезистентність (ІР) метаболічного генезу є патологічним станом, в основі якого лежить зниження метаболічної відповіді інсулін-чутливих клітин на стимуляцію інсуліном. Вона часто супроводжує метаболічно асоційовану жирову хворобу печінки (МАЖХП) і є патогенетичною основою цукрового діабету (ЦД) 2-го типу. МАЖХП пов’язана з високим ризиком ЦД 2-го типу, її наявність збільшує ймовірність виникнення ЦД 2-го типу протягом наступних п’яти років життя хворого приблизно в два рази. У розвитку ІР безпосередню участь беруть довгі некодуючі РНК, визначення рівня експресії яких може суттєво підвищити ефективність діагностики й прогнозу захворювання. На сьогодні серед припущень, що пояснюють механізми виникнення ІР, домінують ліпоцентрична та глюкоцентрична гіпотези. В основі ліпоцентричної гіпотези лежить уявлення про те, що ІР є наслідком ліпотоксичної дії надлишкового внутрішньоклітинного вмісту вільних жирних кислот та їхніх похідних (діацилгліцерин, цераміди). Глюкоцентрична гіпотеза постулює, що розвиток ІР зумовлений рецидивуючими проявами гіперглікемії, які супроводжуються утворенням кінцевих продуктів глікування. Інсулінорезистентна тканина печінки характеризується підвищенням активності глюконеогенезу, виснаженням глікогенового депо та зниженням секреції тригліцеридів. Стеатоз печінки призводить до розвитку ІР, що асоціюється з посиленням активності глюконеогенезу. Селективна ІР печінки є первинною подією в системному порушенні інсулін-асоційованого сигнального шляху, викликаючи в подальшому ІР периферичних тканин. У розвитку печінкової інсулінорезистентності при МАЖХП беруть участь численні некодуючі РНК, як-от H19, MALAT1, MEG3, MIAT, SRA та інші. Довгі некодуючі РНК, рівень експресії яких підвищується в разі інсулінорезистентності печінки: Blnc1, EPB41L4A-AS1, H19, HCG18, HOTAIR, HOTTIP, LncARSR, MAYA, MALAT1, MIAT, NONMMUT031874.2. У той же час довгі некодуючі РНК, рівень експресії яких знижується при розвитку інсулінорезистентності печінки, представлені B4GALT1-AS1/LncSHGL, MEG3.

Insulin resistance (IR) of metabolic origin is a pathological condition, which is based on a decrease in the metabolic response of insulin-sensitive cells to insulin stimulation. It often accompanies metabolically associated fatty liver disease (MAFLD) and is the pathogenetic basis of type 2 diabetes mellitus (T2DM). MAFLD is associated with a high risk of developing T2DM, its presence increases the likelihood of T2DM by approximately two times during the next five years of the patient’s life. Long non-coding RNAs are directly involved in the development of IR, the determination of the level of their expression can significantly increase the effectiveness of diagnosis and prognosis of the disease. Today, among the assumptions explaining the mechanisms of IR development, the lipocentric and glucocentric hypotheses dominate. The lipocentric hypothesis is based on the idea that IR is a consequence of the lipotoxic effect of excessive intracellular content of free fatty acids and their derivatives (diacylglycerol, cera­mides). The glucocentric hypothesis postulates that the development of IR is due to recurrent manifestations of hyperglycemia, which are accompanied by the generation of advanced glycation end products. Insulin-resistant liver tissue is characterized by increased activity of gluconeogenesis, depletion of glycogen depot and decreased secretion of triglycerides. Hepatic steatosis leads to the development of IR, which is accompanied by increased activity of gluconeogenesis. Selective hepatic IR is the primary event in the systemic disruption of the insulin-­associated signaling pathway, which subsequently leads to the development of IR of peripheral tissues. Numerous long non-coding RNAs, such as H19, MALAT1, MEG3, MIAT, SRA, and others, are involved in the development of hepatic insulin resistance in MAFLD. Long non-coding RNAs, the expression level of which increases in case of the development of hepatic insulin resistance, are Blnc1, EPB41L4A-AS1, H19, HCG18, HOTAIR, HOTTIP, LncARSR, MAYA, MALAT1, MIAT, NONMMUT031874.2. At the same time, long non-coding RNAs, the expression level of which decreases hepatic insulin resistance, are represented by B4GALT1-AS1/LncSHGL, MEG3.


Ключевые слова

діти; ожиріння; метаболічно асоційована жирова хвороба печінки; довгі некодуючі РНК; літературний огляд

children; obesity; metabolically associated fatty liver disease; long non-coding RNAs; literature review

doi: http://dx.doi.org/10.22141/2224-0721.21.2.2025.1522

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