Sex-dimorphic hindbrain lactate regulation of ventromedial hypothalamic nucleus glucoregulatory neuron 5'-AMP-activated protein kinase activity and transmitter marker protein expression.
Rats
Female
Male
Animals
Ventromedial Hypothalamic Nucleus
/ metabolism
AMP-Activated Protein Kinases
/ metabolism
Lactic Acid
Rats, Sprague-Dawley
Glucose
/ metabolism
Hypoglycemia
/ metabolism
Rhombencephalon
/ metabolism
Norepinephrine
/ metabolism
Hypoglycemic Agents
Adrenergic Neurons
/ metabolism
AMPK
Corticosterone
L-lactate
Nitric oxide
Norepinephrine
Sex differences
Journal
Neuropeptides
ISSN: 1532-2785
Titre abrégé: Neuropeptides
Pays: Netherlands
ID NLM: 8103156
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
09
06
2022
revised:
16
01
2023
accepted:
29
01
2023
pmc-release:
01
06
2024
medline:
10
5
2023
pubmed:
16
2
2023
entrez:
15
2
2023
Statut:
ppublish
Résumé
The oxidizable glycolytic end-product L-lactate is a gauge of nerve cell metabolic fuel stability that metabolic-sensory hindbrain A2 noradrenergic neurons impart to the brain glucose-regulatory network. Current research investigated the premise that hindbrain lactate deficiency exerts sex-specific control of energy sensor and transmitter marker protein responses to hypoglycemia in ventromedial hypothalamic nucleus (VMN) glucose-regulatory nitrergic and γ-aminobutyric acid (GABA) neurons. Nitric oxide synthase (nNOS)- or glutamate decarboxylase Hindbrain lactate repletion reversed hypoglycemia-associated augmentation (males) or inhibition (females) of nitrergic neuron nNOS expression, and prevented up-regulation of phosphorylated AMPK 5'-AMP-activated protein kinase (pAMPK) expression in those neurons. Hypoglycemic suppression of GABAergic neuron GAD protein was averted by exogenous lactate over the rostro-caudal length of the male VMN and in the middle region of the female VMN. Lactate normalized GABA neuron pAMPK profiles in hypoglycemic male (caudal VMN) and female (all VMN segments) rats. Hypoglycemic patterns of norepinephrine (NE) signaling were lactate-dependent throughout the male VMN, but confined to the rostral and middle female VMN. Results document, in each sex, regional VMN glucose-regulatory transmitter responses to hypoglycemia that are controlled by hindbrain lactate status. Hindbrain metabolic-sensory regulation of hypoglycemia-correlated nitric oxide or GABA release may entail AMPK-dependent mechanisms in specific VMN rostro-caudal segments in each sex. Additional effort is required to examine the role of hindbrain lactoprivic-sensitive VMN neurotransmitters in lactate-mediated attenuation of hypoglycemic hyperglucagonemia and hypercorticosteronemia in male and female rats.
Sections du résumé
BACKGROUND
BACKGROUND
The oxidizable glycolytic end-product L-lactate is a gauge of nerve cell metabolic fuel stability that metabolic-sensory hindbrain A2 noradrenergic neurons impart to the brain glucose-regulatory network. Current research investigated the premise that hindbrain lactate deficiency exerts sex-specific control of energy sensor and transmitter marker protein responses to hypoglycemia in ventromedial hypothalamic nucleus (VMN) glucose-regulatory nitrergic and γ-aminobutyric acid (GABA) neurons.
METHODS
METHODS
Nitric oxide synthase (nNOS)- or glutamate decarboxylase
RESULTS
RESULTS
Hindbrain lactate repletion reversed hypoglycemia-associated augmentation (males) or inhibition (females) of nitrergic neuron nNOS expression, and prevented up-regulation of phosphorylated AMPK 5'-AMP-activated protein kinase (pAMPK) expression in those neurons. Hypoglycemic suppression of GABAergic neuron GAD protein was averted by exogenous lactate over the rostro-caudal length of the male VMN and in the middle region of the female VMN. Lactate normalized GABA neuron pAMPK profiles in hypoglycemic male (caudal VMN) and female (all VMN segments) rats. Hypoglycemic patterns of norepinephrine (NE) signaling were lactate-dependent throughout the male VMN, but confined to the rostral and middle female VMN.
CONCLUSIONS
CONCLUSIONS
Results document, in each sex, regional VMN glucose-regulatory transmitter responses to hypoglycemia that are controlled by hindbrain lactate status. Hindbrain metabolic-sensory regulation of hypoglycemia-correlated nitric oxide or GABA release may entail AMPK-dependent mechanisms in specific VMN rostro-caudal segments in each sex. Additional effort is required to examine the role of hindbrain lactoprivic-sensitive VMN neurotransmitters in lactate-mediated attenuation of hypoglycemic hyperglucagonemia and hypercorticosteronemia in male and female rats.
Identifiants
pubmed: 36791640
pii: S0143-4179(23)00005-7
doi: 10.1016/j.npep.2023.102324
pmc: PMC10175150
mid: NIHMS1871781
pii:
doi:
Substances chimiques
AMP-Activated Protein Kinases
EC 2.7.11.31
Lactic Acid
33X04XA5AT
Glucose
IY9XDZ35W2
Norepinephrine
X4W3ENH1CV
Hypoglycemic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102324Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK109382
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no conflicts of interests to declare.
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