Estrogen receptor-? expressing neurons in the ventrolateral VMH regulate glucose balance.

ABSTRACT: Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Here we report that estrogen receptor-? (ER?)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) can sense glucose fluctuations, being glucose-inhibited neurons (GI-ER?vlVMH) or glucose-excited neurons (GE-ER?vlVMH). Hypoglycemia activates GI-ER?vlVMH neurons via the anoctamin 4 channel, and inhibits GE-ER?vlVMH neurons through opening the ATP-sensitive potassium channel. Further, we show that GI-ER?vlVMH neurons preferentially project to the medioposterior arcuate nucleus of the hypothalamus (mpARH) and GE-ER?vlVMH neurons preferentially project to the dorsal Raphe nuclei (DRN). Activation of ER?vlVMH to mpARH circuit and inhibition of ER?vlVMH to DRN circuit both increase blood glucose. Thus, our results indicate that ER?vlVMH neurons detect glucose fluctuations and prevent severe hypoglycemia in mice.

SUBMITTER: He Y 

PROVIDER: S-EPMC7195451 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature