Short-term fasting differentially regulates PI3K/AkT/mTOR and ERK signalling in the rat hypothalamus

Abstract

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.