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Роль и регуляция индуцируемого гипоксией фактора транскрипции-1 и сукцинатного рецептора-1 при диабете типа 2: связь с сосудистыми осложнениями

https://doi.org/10.33647/2074-5982-15-1-48-61

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Аннотация

Диабет 2 типа является основным метаболическим заболеванием, которое со временем приводит к серьезным осложнениям. Жесткий контроль уровней глюкозы в крови считается важной мерой, позволяющей предотвратить осложнения диабета. Однако рандомизированные клинические испытания, проведенные за последние десятилетия, не выявили существенной пользы гликемического контроля для предотвращения микро- и макрососудистых осложнений диабета, за исключением снижения риска нефатального инфаркта миокарда на 15%. В то же время появляются данные, что существует корреляция между возникновением сосудистых осложнений сахарного диабета и нарушениями в регуляции ангиогенеза управляемой индуцируемым гипоксией фактором 1 (HIF-1) и сукцинатным рецептором 1 (SUCNR1). Диабет 2 типа влияет на активность HIF-1 на нескольких уровнях, включая транскрипцию субъединицы HIF-1α, трансляцию мРНК в белок HIF-1α, деградацию белка HIF-1α и связывание белка HIF-1α с коактиваторами, что в итоге приводит к нарушению адаптивного ангиогенного ответа на гипоксию. Гипергликемия и инсулиновая резистентность участвуют в этих нарушениях. Кроме того, диабет влияет на передачу сигналов сукцинатного рецептора 1 тканеспецифическим образом. Перекрестное взаимодействие между HIF-1 и SUCNR1 объясняет, по крайней мере частично, парадоксальные тканеспецифические изменения ангиогенеза при диабетических микрососудистых осложнениях, а именно чрезмерное образование кровеносных сосудов в сетчатке и дефицит мелких кровеносных сосудов в периферических тканях, таких как кожа. В заключение, терапевтическое воздействие на сигнальные системы HIF-1 и SUCNR1 может стать новым многообещающим подходом к профилактике и лечению сосудистых осложнений диабета 2 типа.

Об авторах

И. А. Помыткин
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский университет)
Россия
119991, Москва, ул. Трубецкая, д. 8, стр. 2


В. Н. Каркищенко
ФГБУН «Научный центр биомедицинских технологий Федерального медико-биологического агентства России»
Россия

д.м.н., проф.,

143442, Московская обл., Красногорский р-н, п. Светлые горы, владение 1



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Для цитирования:


Помыткин И.А., Каркищенко В.Н. Роль и регуляция индуцируемого гипоксией фактора транскрипции-1 и сукцинатного рецептора-1 при диабете типа 2: связь с сосудистыми осложнениями. БИОМЕДИЦИНА. 2019;(1):48-61. https://doi.org/10.33647/2074-5982-15-1-48-61

For citation:


Pomytkin I.A., Karkischenko V.N. The role and regulation of hypoxia-inducible transcription factor-1 and succinate receptor-1 in type 2 diabetes: a link to vascular complications. Journal Biomed. 2019;(1):48-61. https://doi.org/10.33647/2074-5982-15-1-48-61

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