Insulin signalling in tanycytes gates hypothalamic insulin uptake and regulation of AgRP neuron activity.

ABSTRACT: Insulin acts on neurons and glial cells to regulate systemic glucose metabolism and feeding. However, the mechanisms of insulin access in discrete brain regions are incompletely defined. Here we show that insulin receptors in tanycytes, but not in brain endothelial cells, are required to regulate insulin access to the hypothalamic arcuate nucleus. Mice lacking insulin receptors in tanycytes (IR^∆Tan mice) exhibit systemic insulin resistance, while displaying normal food intake and energy expenditure. Tanycytic insulin receptors are also necessary for the orexigenic effects of ghrelin, but not for the anorexic effects of leptin. IR^∆Tan mice exhibit increased agouti-related peptide (AgRP) neuronal activity, while displaying blunted AgRP neuronal adaptations to feeding-re

SUBMITTER: Porniece Kumar M 

PROVIDER: S-EPMC8688146 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature