ВЛИЯНИЕ ИНТРАНАЗАЛЬНО ВВОДИМЫХ ИНСУЛИНА И ГАНГЛИОЗИДОВ НА МЕТАБОЛИЧЕСКИЕ ПОКАЗАТЕЛИ И АКТИВНОСТЬ ИНСУЛИНОВОЙ СИСТЕМЫ В ПЕЧЕНИ КРЫС С САХАРНЫМ ДИАБЕТОМ 2-ГО ТИПА
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Ключевые слова

инсулин
ганглиозиды
интраназальное введение
сахарный диабет 2-го типа
печень
Akt-киназа
киназа гликогенсинтазы-3β
глюкозотолерантность

Аннотация

Регуляция метаболизма глюкозы инсулином осуществляется как за счет прямого взаимодействия гормона с его сигнальной системой и транспортерами глюкозы в клетках периферических тканей, так и опосредованно через центральную нервную систему (ЦНС). При сахарном диабете 2-го типа (СД2) наблюдается недостаток инсулина в мозге вследствие нарушенного рецептор-опосредуемого транспорта гормона через гематоэнцефалический барьер, что приводит к дисфункциям пищевого поведения, термогенеза, метаболизма углеводов и жиров. Использование интраназально вводимого инсулина (ИВИ) позволяет увеличить его содержание в мозге. ИВИ в комплексе с различными сенситизаторами обеспечивает восстановление толерантности к глюкозе за более короткий срок при меньших дозах инсулина. Комбинированная терапия в виде ИВИ (0.5 МЕ/крысу/сутки) крысам с СД2 и суммарных ганглиозидов мозга теленка (6 мг/кг/сутки) использовалась впервые. Через 4 недели у животных с СД2 после совместного интраназального введения инсулина и ганглиозидов восстанавливалась толерантность к глюкозе, в то время как по отдельности препараты были менее эффективны. С помощью Вестерн-блоттинга было показано, что увеличение чувствительности к инсулину в печени может быть обусловлено значительным снижением экспрессии негативного регулятора инсулинового сигналинга протеинфосфотирозинфосфатазы РТР1В и увеличением степени фосфорилирования ключевых эффекторных протеинкиназ Akt по Ser473, GSK3β по Ser9 и р38-МАРК по Thr180/Tyr182. При этом ингибирующее фосфорилирование GSK3β по Ser9 может осуществляться как вследствие активации Akt-киназы, так и р38-МАРК, и вклад последней, как мы полагаем, более значимый. Поскольку инсулин и ганглиозиды при интраназальном введении непосредственно воздействовали на структуры мозга, компетентные в отношении регуляции периферической инсулиновой чувствительности и углеводного обмена в печени, сделан вывод о превалировании в этом случае центрального механизма их действия.

https://doi.org/10.31857/S0044452922020085
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