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.

众所周知，胰腺β细胞分泌的胰岛素通过血脑屏障进入大脑。然而，已经证明胰岛素表达也发生在不同的大脑区域。尽管大脑中胰岛素作用的清单很长，包括控制能量稳态、神经元存活、维持突触可塑性和认知，但对大脑中胰岛素合成的适应性意义知之甚少。

我们之前报道过短期禁食会促进大鼠脑室周围核中胰岛素的表达和随后的胰岛素受体的激活。为了揭示禁食诱导的下丘脑胰岛素表达的生理重要性，我们分析了短期食物剥夺对 PI3K/AKT/mTOR 和 Ras/MAPK 信号通路的几个参与者表达的影响，这些信号通路通常由这种激素。

我们发现下丘脑总和激活的 IRS1、IRS2、PI3K 和 mTOR 的含量保持不变，但磷酸化的 AKT1/2/3 降低。禁食 6 小时后激活的 ERK1/2 水平增加。此外，激活的 ERK1/2 与弓状核中激活的胰岛素受体共表达。我们之前发表的和当前的研究结果表明，下丘脑的 ERK 激活至少部分是由中枢产生的胰岛素启动的。