Department for Comparative Physiology and Ecophysiology, Institute for Physiology and Biochemistry "Ivan Djaja", University of Belgrade-Faculty of Biology, Studentski trg 16, 11000 Belgrade, Republic of Serbia.
Department for Comparative Physiology and Ecophysiology, Institute for Physiology and Biochemistry "Ivan Djaja", University of Belgrade-Faculty of Biology, Studentski trg 16, 11000 Belgrade, Republic of Serbia.
Mech Ageing Dev. 2020 Dec;192:111358. doi: 10.1016/j.mad.2020.111358. Epub 2020 Sep 19.
It is known that insulin secreted by pancreatic β-cells enters the brain by crossing the blood-brain barrier. However, it was demonstrated that insulin expression occurs in various brain regions as well. Albeit the list of insulin actions in the brain is long and it includes control of energy homeostasis, neuronal survival, maintenance of synaptic plasticity and cognition, not much is known about the adaptive significance of insulin synthesis in brain. We previously reported that short-term fasting promotes insulin expression and subsequent activation of insulin receptor in the rat periventricular nucleus. In order to uncover a physiological importance of the fasting-induced insulin expression in hypothalamus, we analyzed the effect of short-term food deprivation on the expression of several participants of PI3K/AKT/mTOR and Ras/MAPK signaling pathways that are typically activated by this hormone. We found that the hypothalamic content of total and activated IRS1, IRS2, PI3K, and mTOR remained unchanged, but phosphorylated AKT1/2/3 was decreased. The levels of activated ERK1/2 were increased after six-hour fasting. Moreover, activated ERK1/2 was co-expressed with activated insulin receptor in the nucleus arcuatus. Our previously published and current findings suggest that the ERK activation in hypothalamus was at least partially initiated by the centrally produced insulin.
已知胰岛β细胞分泌的胰岛素通过血脑屏障进入大脑。然而，也有研究表明，胰岛素在大脑的不同区域表达。尽管胰岛素在大脑中的作用很多，包括控制能量稳态、神经元存活、维持突触可塑性和认知，但对于大脑中胰岛素合成的适应意义知之甚少。我们之前的研究报告表明，短期禁食会促进大鼠室旁核中胰岛素的表达和胰岛素受体的后续激活。为了揭示下丘脑内禁食诱导的胰岛素表达的生理重要性，我们分析了短期禁食对 PI3K/AKT/mTOR 和 Ras/MAPK 信号通路中几个参与者表达的影响，这些通路通常会被这种激素激活。我们发现，下丘脑内总 IRS1、IRS2、PI3K 和 mTOR 的含量以及激活的 IRS1、IRS2、PI3K 和 mTOR 含量保持不变，但磷酸化 AKT1/2/3 减少。经过六小时禁食后，激活的 ERK1/2 水平增加。此外，激活的 ERK1/2 在弓状核中与激活的胰岛素受体共表达。我们之前发表的和目前的研究结果表明，下丘脑内的 ERK 激活至少部分是由中枢产生的胰岛素启动的。
