Glucose-sensing glucagon-like peptide-1 receptor neurons in the dorsomedial hypothalamus regulate glucose metabolism

Abstract

Glucagon-like peptide-1 (GLP-1) regulates energy homeostasis via activation of the GLP-1 receptors (GLP-1Rs) in the central nervous system. However, the mechanism by which the central GLP-1 signal controls blood glucose levels, especially in different nutrient states, remains unclear. Here, we defined a population of glucose-sensing GLP-1R neurons in the dorsomedial hypothalamic nucleus (DMH), by which endogenous GLP-1 decreases glucose levels via the cross-talk between the hypothalamus and pancreas. Specifically, we illustrated the sufficiency and necessity of DMH GLP-1R in glucose regulation. The activation of the DMH GLP-1R neurons is mediated by a cAMP-PKA–dependent inhibition of a delayed rectifier potassium current. We also dissected a descending control of DMH GLP-1R –dorsal motor nucleus of the vagus nerve (DMV)–pancreas activity that can regulate glucose levels by increasing insulin release. Thus, our results illustrate how central GLP-1 action in the DMH can induce a nutrient state–dependent reduction in blood glucose level.

Body temperature regulates glucose metabolism and torpid behavior

“…Moreover, the stable and fasting-disregard blood glucose levels and hyperinsulinemia suggest that the reorganized glucose homeostasis in QIH is not responsive to body energy states. The brain particularly hypothalamic nuclei such as the ARC, ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), and PVN play a critical role in sensing blood glucose, which can reflect energy levels to regulate whole-body energy metabolism (Alvarsson and Stanley, 2018; Huang et al, 2022; Shimazu and Minokoshi, 2017). We showed that QIH universally silences neuronal activity, at least in the ARC.…”

Body temperature regulates glucose metabolism and torpid behavior

“…Moreover, the stable and fasting-disregard blood glucose levels and hyperinsulinemia suggest that the reorganized glucose homeostasis in QIH is not responsive to body energy states. The brain particularly hypothalamic nuclei such as the ARC, ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), and PVN play a critical role in sensing blood glucose, which can reflect energy levels to regulate whole-body energy metabolism 10,29,30 . We showed that QIH universally silences neuronal activity, at least in the ARC.…”

Blood‐Glucose‐Powered Metabolic Fuel Cell for Self‐Sufficient Bioelectronics

“…Ideally, it would be preferable to operate bioelectronic implants using an endogenous power source for self‐sufficient, continuous, and reliable operation. In principle, body fluids contain sufficient excess metabolic energy in the form of fatty acids, [ 56 ] and glucose, [ 57 ] which could be harnessed to power bioelectronic implants as well as wearable electronic devices. Since fatty acid metabolism is functionally linked with glucose production via gluconeogenesis.…”