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Успехи физиологических наук, 2023, T. 54, № 2, стр. 86-104

ГАМК-ергическая система в регуляции функционирования бета-клеток поджелудочной железы в условиях нормы и при сахарном диабете

И. Н. Тюренков a, Т. И. Файбисович b, М. А. Дубровина a, Д. А. Бакулин a, *, Д. В. Куркин a

a ФГБОУ Волгоградский Государственный медицинский университет
400087 Волгоград, Россия

b ФГБВОУ ВО Военно-медицинская академия им. С.М. Кирова МО РФ
194044 Санкт-Петербург, Россия

* E-mail: mbfdoc@gmail.com

Поступила в редакцию 20.11.2022
После доработки 15.01.2023
Принята к публикации 18.01.2023

Аннотация

Заболеваемость сахарным диабетом (СД) во всем мире неуклонно растет, а вместе с этим отмечается рост его осложнений, которые являются главными причинами ранней инвалидизации и преждевременной смерти. В основе патогенеза СД лежит неуклонное уменьшение числа β-клеток поджелудочной железы при СД 1 типа до 30–10%, при СД 2 типа до 50–40% от нормального количества. Уменьшение β-клеточной массы ведет к снижению продукции инсулина и развитию гипергликемии и связанных с ней тяжелых осложнений. Поэтому очевидна необходимость предупреждения гибели β-клеток и стимуляции их регенерации. В зарубежной литературе последнего времени уделяется большое внимание роли ГАМК в регуляции функции α- и β-клеток поджелудочной железы и углеводного обмена, что в отечественной литературе практически не отражено, чему и посвящен данный обзор. Гамма-аминомасляная кислота (ГАМК) в β-клетках и островках поджелудочной железы определяется в количествах, сопоставимых с содержанием в головном мозге. Там же содержится и высокое количество глутамадекарбоксилазы – фермента, синтезирующего ГАМК. При СД уровень ГАМК в β-клетках поджелудочной железы снижается и это коррелирует с тяжестью нарушений углеводного обмена. ГАМК играет важную роль в паракринной регуляции функций α- и β-клеток, углеводного гомеостаза. Доказана потенциальная возможность с помощью ГАМК добиться снижения апоптоза и, одновременно, усиления регенерации β-клеток, увеличения β-клеточной массы поджелудочной железы, повышения секреции инсулина, адекватного контроля уровня глюкозы в организме. Доказано, что положительное влияние ГАМК на структуру и функции β-клеток поджелудочной железы при СД может быть существенно выше при совместном применении с антидиабетическими средствами: агонистами рецептора ГПП-1, ингибиторами ДПП-4, ингибиторами SGLT-2 и другими. Антидиабетические свойства ГАМК объясняются ее взаимодействием с различными сигнальными белками (белком Клото, SIRT, PI3K/Akt, CREB-IRS2, NF-kB, Nrf2 и многими другими), посредством модуляции которых эти эффекты реализуются. Данные о панкреопротективном действии ГАМК и ее производных могут лечь в основу разработки новой фармакотерапевтической стратегии лечения СД и сопряженных с ними осложнений.

Ключевые слова: ГАМК, β-клетки, α-клетки, сахарный диабет, апоптоз, ГАМКА, ГАМКВ

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