Аннотация
Инсулиновая сигнальная система в гипоталамических нейронах играет важную роль в центральной регуляции метаболизма глюкозы, пищевого поведения и чувствительности тканей к инсулину. Снижение содержания инсулина в мозге при метаболических расстройствах, в том числе при диабете, является причиной низкой активности ключевых протеинкиназ, регулируемых через инсулиновую систему. Недостаток гормона в мозге, может быть компенсирован за счет интраназально вводимого инсулина, который доставляется непосредственную в мозг. Его эффективность может быть повышена посредством совместного использования с веществами, усиливающими действие инсулина в мозге, к числу которых принадлежат сложные гликосфинголипиды ганглиозиды. Целью работы было изучить влияние раздельного и совместного интраназального введения инсулина (0.5 МЕ/крысу/сутки) и ганглиозидов (6 мг/кг/сутки) крысам линии Wistar с экспериментальным сахарным диабетом 2-го типа (СД2) на активность ключевых компонентов инсулинового сигналинга (Akt, GSK-3β, ERK1/2, p70S6K и AMPK) в гипоталамусе, а также на экспрессию генов (GLUT2, FASN, PCK, G6PC и FBP), ответственных за метаболизм глюкозы в печени. Впервые установлено, что совместные интраназальные введения инсулина и ганглиозидов крысам с СД2 приводят к восстановлению толерантности к глюкозе, улучшению чувствительности тканей к инсулину, усилению обменных процессов и подавлению глюконеогенеза в гепатоцитах печени. Это происходит во многом благодаря центральному синхронизированному влиянию инсулина и ганглиозидов на функциональную активность ключевых белков инсулинового сигналинга (GSK3β, p70S6K, ERK1/2, AMPK) в гипоталамусе, а также вследствие восстановления экспрессии BDNF и снижения мРНК воспалительного цитокина IL-1β в гипоталамических нейронах. Таким образом, совместное интраназальное введение инсулина и ганглиозидов крысам с СД2 в значительной степени восстанавливает у них инсулиновый сигналинг в гипоталамусе и контроль глюконеогенеза в печени, нарушенные в условиях диабетической патологии.
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