The hypothalamus as a key regulator of glucose homeostasis: emerging roles of the brain renin-angiotensin system

Abstract

The regulation of plasma glucose levels is a complex and multifactorial process involving a network of receptors and signaling pathways across numerous organs that act in concert to ensure homeostasis. However, much about the mechanisms and pathways by which the brain regulates glycemic homeostasis remains poorly understood. Understanding the precise mechanisms and circuits employed by the central nervous system to control glucose is critical to resolving the diabetes epidemic. The hypothalamus, a key integrative center within the central nervous system, has recently emerged as a critical site in the regulation of glucose homeostasis. Here, we review the current understanding of the role of the hypothalamus in regulating glucose homeostasis, with an emphasis on the paraventricular nucleus, the arcuate nucleus, the ventromedial hypothalamus, and lateral hypothalamus. In particular, we highlight the emerging role of the brain renin-angiotensin system in the hypothalamus in regulating energy expenditure and metabolic rate, as well as its potential importance in the regulation of glucose homeostasis.

(Pro)renin receptor signaling in hypothalamic tyrosine hydroxylase neurons is required for obesity-associated glucose metabolic impairment

“…The hypothalamic PVN comprises multiple neuronal subpopulations, including many neuroendocrine and preautonomic neurons that play critical roles in various physiological processes ( 43 – 45 ), including glucose homeostasis ( 46 ). Compared with PVN neurons involved in the control of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes (expressing CRH and TRH, respectively), as well as neurons expressing oxytocin or vasopressin, however, TH-containing neurons in this brain area have received limited attention.…”

“…Based on our finding that the blood glucose level is rapidly elevated following their chemogenetic inhibition, PVN TH neurons join the growing list of hypothalamic neurons implicated as contributors to the biologically defended level of glycemia ( 3 , 46 ). We also present electrophysiological evidence that PRR activation exerts a direct, inhibitory effect on PVN TH neurons that does not require synaptic transmission.…”