Перспективные фармакологические мишени для лечения заболеваний, сопряженных с дефектом сигнального пути рецептора инсулина

Сахарный диабет (СД) занимает одно из первых мест в мире среди наиболее распространенных хронических заболеваний. При СД 2-го типа (СД2) наблюдается стойкая инсулинорезистентность, обусловленная нарушением способности гормона стимулировать захват глюкозы клетками-мишенями и снижать уровень глюкозы в крови. В основе этого лежит, вероятнее всего, нарушение передачи сигнала от рецептора инсулина (ИР) к внутриклеточным инсулинзависимым сигнальным каскадам. Оптимизация существующих и разработка ранее не задействованных подходов к терапии СД позволяет считать актуальной задачей поиск новых мишеней для создания инновационных антидиабетических соединений. Среди множества возможных мишеней особое место занимает ИР и ассоциированные с ним сигнальные пути. В обзоре уделяется внимание строению ИР и функционированию сопряженных с ним сигнальных путей. Представлены данные о новых лигандах-миметиках и сенситайзерах ИР, а также о других молекулах, способных влиять на различные компоненты сопряженных с ИР сигнальных путей, тем самым проявляющих конкретный антидиабетический эффект. Действие данных соединений направлено на коррекцию основных метаболических нарушений, приводящих к гипергликемии, и условно сводится к следующим эффектам: активации и потенцированию инсулиновой сигнализации, улучшению чувствительности периферических тканей к инсулину; восстановлению физиологических механизмов секреции инсулина; снижению повышенной продукции глюкозы печенью.

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