Глюкокиназа: эволюция, регуляторные свойства, роль в патогенезе сахарного диабета

В обзоре рассмотрены вопросы эволюции, структурно-функциональной организации и регуляторные свойства глюкокиназы, которая преимущественно экспрессируется в β-клетках поджелудочной железы и в гепатоцитах печени. Значительное внимание уделено возможной роли глюкокиназы в этиологии и патогенезе сахарного диабета 2 типа (СД2), и разработке подходов для нормализации секреции инсулина, глюкозного гомеостаза, углеводного и липидного обмена с помощью регуляторов активности глюкокиназы. Представлены данные о влиянии вариантов в гене глюкокиназы и регуляторного белка глюкокиназы в развитии нарушений инсулин-секретирующей функции поджелудочной железы. Так инактивирующие мутации в гене глюкокиназы вызывают СД2, в то время как активирующие мутации приводят к врожденному гиперинсулинизму. Обсуждаются данные, что L-аргинин, аллостерически взаимодействуя с глюкокиназой, стимулирует секрецию инсулина и ингибирует деградацию фермента, защищая его от убиквитинирования. Сделан вывод, что глюкокиназа и функционально связанные с ней белки являются перспективными мишенями при разработке подходов для нормализации чувствительности панкреатических β-клеток к глюкозе, восстановления секреции инсулина и глюкозного гомеостаза при СД2 и других метаболических расстройствах. Данные для этого обзора были определены путем поиска в MEDLINE, PubMed и ссылках на статьи, опубликованные на английском и русском языках в период с 1966 по 2024 год.

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