Физиология и фармакология рецептора глюкагоноподобного пептида-1

Современные подходы к лечению сахарного диабета 2 типа (СД2) направлены не только на контроль гликемии, но и на снижение кардиоваскулярных рисков. Рост распространенности заболевания и необходимость в эффективных вариантах лечения подчеркивают важность агонистов рецепторов глюкагоноподобного пептида-1 (ГПП-1) в структуре фармакотерапии.

Цель. Анализ литературы, касающейся физиологии ГПП-1, а также терапевтического потенциала и тенденций развития его агонистов.

Материалы и методы. Поиск материала для написания обзора проводили с использованием реферативных баз PubMed, Google Scholar и e-Library. Поиск осуществляли по публикациям в период с 2000 по 2023 годы, с использованием следующих ключевых слов: «ГПП-1»; «агонисты ГПП-1Р»; «ГИП»; «эксенатид»; «лираглутид»; «дулаглутид»; «семаглутид»; «ликсисенатид»; «албиглутид»; «таспоглутид» с учетом различных вариантов их написания.

Результаты. Взаимодействие практически всех компонентов пищи с энтероэндокринными клетками кишечника приводит к секреции в кровь инкретинов (прежде всего ГПП-1), запускающих комплекс физиологических реакций, направленных, в первую очередь, на быструю утилизацию поступающей глюкозы (регуляция секреции инсулина и глюкагона), а также центральную регуляцию пищевого поведения (замедление опорожнения желудка и формирование чувства насыщения). Широкое распространение рецептора к ГПП-1 в различных тканях и органах, его связь с внутриклеточными сигнальными каскадами, направленными на запуск энергозатратных процессов ремоделирования (восстановления) в клетках эндотелия, сердца, нейронах, бета-клетках и др., является основой для широкого спектра плейотропных эффектов ГПП-1, не связанных с его гипогликемическим действием. Открытие синтетических агонистов рецепторов ГПП-1 с длительным периодом действия дало возможность не только терапевтически воздействовать на различные звенья нарушений углеводного обмена, но и увеличить функциональные резервы органов-мишеней СД, снижая риск развития осложнений заболевания. Инкретиноподобные препараты хорошо переносятся, самым распространенным побочным эффектом является тошнота. Факторы, ограничивающие более широкое использование препаратов, включают высокую стоимость и преимущественную форму – раствор для подкожного введения. Текущие исследования связаны с разработкой препаратов с пролонгированным действием, пероральной формы, двойных и тройных агонистов, фиксированных комбинаций, а также препаратов малых молекул.

Заключение. Агонисты рецепторов ГПП-1 представляют собой класс эффективных и безопасных лекарственных средств для терапии СД и ожирения, который стремительно развивается по самым передовым направлениям фармации. Дальнейшее развитие этой группы и решение обозначенных задач откроет новые возможности для лечения СД и его осложнений.

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