PMID- 37194319
OWN - NLM
STAT- MEDLINE
DCOM- 20230518
LR  - 20230525
IS  - 1759-0914 (Electronic)
IS  - 1759-0914 (Linking)
VI  - 15
DP  - 2023 Jan-Dec
TI  - Sex-Dimorphic Octadecaneuropeptide (ODN) Regulation of Ventromedial Hypothalamic 
      Nucleus Glucoregulatory Neuron Function and Counterregulatory Hormone Secretion.
PG  - 17590914231167230
LID - 10.1177/17590914231167230 [doi]
LID - 17590914231167230
AB  - Central endozepinergic signaling is implicated in glucose homeostasis. 
      Ventromedial hypothalamic nucleus (VMN) metabolic monitoring governs glucose 
      counter-regulation. VMN glucose-stimulatory nitric oxide (NO) and 
      glucose-inhibitory gamma-aminobutyric acid (GABA) neurons express the energy gauge 
      5'-AMP-activated protein kinase (AMPK). Current research addresses the premise 
      that the astrocyte glio-peptide octadecaneuropeptide (ODN) imposes sex-dimorphic 
      control of metabolic sensor activity and neurotransmitter signaling in these 
      neurons. The ODN G-protein coupled-receptor antagonist cyclo((1-8))[DLeu(5)]OP 
      (LV-1075) was administered intracerebroventricularly (icv) to euglycemic rats of 
      each sex; additional groups were pretreated icv with the ODN isoactive surrogate 
      ODN(11-18) (OP) before insulin-induced hypoglycemia. Western blotting of 
      laser-catapult-microdissected VMN NO and GABA neurons showed that hypoglycemia 
      caused OP-reversible augmentation of phospho-, e.g., activated AMPK and nitric 
      oxide synthase (nNOS) expression in rostral (female) or middle (male) VMN 
      segments or ODN-dependent suppression of nNOS in male caudal VMN. OP prevented 
      hypoglycemic down-regulation of glutamate decarboxylase profiles in female rat 
      rostral VMN, without affecting AMPK activity. LV-1075 treatment of male, not 
      female rats elevated plasma glucagon and corticosterone concentrations. Moreover, 
      OP attenuated hypoglycemia-associated augmentation of these hormones in males 
      only. Results identify, for each sex, regional VMN metabolic transmitter signals 
      that are subject to endozepinergic regulation. Directional shifts and 
      gain-or-loss of ODN control during eu- versus hypoglycemia infer that VMN neuron 
      receptivity to or post-receptor processing of this stimulus may be modulated by 
      energy state. In male, counter-regulatory hormone secretion may be governed 
      principally by ODN-sensitive neural pathways, whereas this endocrine outflow may 
      be controlled by parallel, redundant ODN-dependent and -independent mechanisms in 
      female.
FAU - Briski, Karen P
AU  - Briski KP
AUID- ORCID: 0000-0002-7648-1395
AD  - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, 
      University of Louisiana Monroe, Monroe, LA, USA.
FAU - Napit, Prabhat R
AU  - Napit PR
AD  - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, 
      University of Louisiana Monroe, Monroe, LA, USA.
FAU - Alhamyani, Abdulrahman
AU  - Alhamyani A
AD  - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, 
      University of Louisiana Monroe, Monroe, LA, USA.
FAU - Leprince, Jerome
AU  - Leprince J
AUID- ORCID: 0000-0002-7814-9927
AD  - Neuronal and Neuroendocrine Differentiation and Communication Laboratory, 
      Normandy University, INSERM U1239, PRIMACEN, Rouen, France.
FAU - Mahmood, A S M Hasan
AU  - Mahmood ASMH
AD  - School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, 
      University of Louisiana Monroe, Monroe, LA, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - ASN Neuro
JT  - ASN neuro
JID - 101507115
RN  - 0 (diazepam binding inhibitor (33-50))
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 9005-79-2 (Glycogen)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Hormones)
SB  - IM
MH  - Rats
MH  - Male
MH  - Animals
MH  - *Ventromedial Hypothalamic Nucleus
MH  - Rats, Sprague-Dawley
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Glycogen/metabolism
MH  - Norepinephrine/pharmacology
MH  - Glucose/metabolism
MH  - *Hypoglycemia/chemically induced/metabolism
MH  - Neurons/metabolism
MH  - Hormones/metabolism/pharmacology
PMC - PMC10196551
OTO - NOTNLM
OT  - AMPK
OT  - cyclo(1-8)[DLeu5]OP
OT  - insulin-induced hypoglycemia
OT  - neuronal nitric oxide synthase
OT  - octadecaneuropeptide
OT  - sex differences
OT  - ventromedial hypothalamic nucleus
COIS- The author(s) declared no potential conflicts of interest with respect to the 
      research, authorship, and/or publication of this article.
EDAT- 2023/05/17 06:42
MHDA- 2023/05/18 06:42
PMCR- 2023/05/17
CRDT- 2023/05/17 03:42
PHST- 2023/05/18 06:42 [medline]
PHST- 2023/05/17 06:42 [pubmed]
PHST- 2023/05/17 03:42 [entrez]
PHST- 2023/05/17 00:00 [pmc-release]
AID - 10.1177_17590914231167230 [pii]
AID - 10.1177/17590914231167230 [doi]
PST - ppublish
SO  - ASN Neuro. 2023 Jan-Dec;15:17590914231167230. doi: 10.1177/17590914231167230.