Central Type II Glucocorticoid Receptor Regulation of Ventromedial Hypothalamic Nucleus Glycogen Metabolic Enzyme and Glucoregulatory Neurotransmitter Marker Protein Expression in the Male Rat.
Dexamethasone
Glucocorticoid receptor
Glycogen phosphorylase
Nitric oxide synthase
RU486
Ventromedial hypothalamic nucleus
Journal
Journal of endocrinology and diabetes
ISSN: 2374-6890
Titre abrégé: J Endocrinol Diabetes
Pays: United States
ID NLM: 101648451
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
14
7
2021
pubmed:
1
1
2020
medline:
1
1
2020
Statut:
ppublish
Résumé
The ventromedial hypothalamic nucleus (VMN) glucoregulatory neurotransmitters γ-aminobutyric acid (GABA) and nitric oxide (NO) signal adjustments in glycogen mobilization. Glucocorticoids control astrocyte glycogen metabolism in vitro. The classical (type II) glucocorticoid receptor (GR) is expressed in key brain structures that govern glucostasis, including the VMN. Current research addressed the hypothesis that forebrain GR regulation of VMN glycogen synthase (GS) and phosphorylase (GP) protein expression correlates with control of glucoregulatory transmission. Groups of male rats were pretreated by intracerebroventricular (icv) delivery of the GR antagonist RU486 or vehicle prior to insulin-induced hypoglycemia (IIH), or were pretreated icv with dexamethasone (DEX) or vehicle before subcutaneous insulin diluent injection. DEX increased VMN GS and norepinephrine-sensitive GP-muscle type (GPmm), but did not alter metabolic deficit-sensitive GP-brain type (GPbb) expression. RU486 enhanced GS and GPbb profiles during IIH. VMN astrocyte (MCT1) and neuronal (MCT2) monocarboxylate transporter profiles were up-regulated in euglycemic and hypoglycemic animals by DEX or RU486, respectively. Glutamate decarboxylase65/67 and neuronal nitric oxide synthase (nNOS) proteins were both increased by DEX, yet RU486 augmented hypoglycemic nNOS expression patterns. Results show that GR exert divergent effects on VMN GS, MCT1/2, and nNOS proteins during eu- (stimulatory) versus hypoglycemia (inhibitory); these findings imply that up-regulated NO transmission may reflect, in part, augmented glucose incorporation into glycogen and/or increased tissue lactate requirements. Data also provide novel evidence for metabolic state-dependent GR regulation of VMN GPmm and GPbb profiles; thus, GABA signaling of metabolic stability may reflect, in part, stimulus-specific glycogen breakdown during eu- versus hypoglycemia.
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK109382
Pays : United States
Déclaration de conflit d'intérêts
Declaration of interest The authors have no interests to declare.
Références
J Neurochem. 2004 Feb;88(4):900-8
pubmed: 14756811
Diabetes. 2003 Mar;52(3):663-6
pubmed: 12606506
Nature. 1969 Apr 19;222(5190):282-4
pubmed: 5778398
Diabetes. 2010 Feb;59(2):519-28
pubmed: 19934009
J Biol Chem. 2018 May 11;293(19):7099-7107
pubmed: 29483194
Physiol Rep. 2017 Dec;5(23):
pubmed: 29199177
J Endocrinol. 1987 Dec;115(3):459-67
pubmed: 3443807
Front Cell Neurosci. 2013 Apr 10;7:38
pubmed: 23596393
Diabetes. 2013 Dec;62(12):4239-46
pubmed: 23939392
Nature. 1989 Aug 24;340(6235):609-16
pubmed: 2770867
Diabetes. 2006 Apr;55(4):1080-7
pubmed: 16567532
Neuropeptides. 2018 Dec;72:65-74
pubmed: 30396594
J Neurosci Res. 2017 Jul;95(7):1427-1437
pubmed: 27618227
Neurosci Biobehav Rev. 2000 May;24(3):295-340
pubmed: 10781693
Am J Physiol. 1994 Jan;266(1 Pt 1):E118-28
pubmed: 8304437
Neuroendocrinology. 1995 Jun;61(6):638-45
pubmed: 7659189
Endocr Rev. 1998 Jun;19(3):269-301
pubmed: 9626555
Mol Cell Neurosci. 2019 Mar;95:51-58
pubmed: 30660767
Neuroscience. 2015 Apr 30;292:34-45
pubmed: 25701713
Endocrinology. 1986 Jul;119(1):159-67
pubmed: 2873024
Handb Clin Neurol. 2013;117:295-307
pubmed: 24095133
Neuroscience. 2018 Jul 15;383:46-59
pubmed: 29746990
Eur J Biochem. 1976 Jan 2;61(1):243-51
pubmed: 173552
Exp Brain Res. 2007 Jan;176(2):260-6
pubmed: 16850320
Adv Exp Med Biol. 2017;1043:359-383
pubmed: 29224103
J Biol Chem. 1997 Nov 28;272(48):30096-102
pubmed: 9374487
Curr Top Med Chem. 2008;8(9):813-38
pubmed: 18537690
Acta Neuropathol. 1984;64(3):177-91
pubmed: 6496035
Physiology (Bethesda). 2014 Sep;29(5):314-24
pubmed: 25180261
Brain Res. 2019 May 15;1711:48-57
pubmed: 30629946
J Biol Chem. 1967 Jan 25;242(2):271-80
pubmed: 6016612
Neurotox Res. 2010 Jul;18(1):94-9
pubmed: 20306167
Endocrinology. 2015 Aug;156(8):2843-53
pubmed: 26046806
Pflugers Arch. 1990 Jan;415(4):479-83
pubmed: 2315006
Front Neuroendocrinol. 2010 Jan;31(1):32-43
pubmed: 19836412
Endocrinology. 1993 Nov;133(5):1941-50
pubmed: 8404640
Diabetes. 2014 Jul;63(7):2188-95
pubmed: 24962915
Can J Physiol Pharmacol. 1990 Sep;68(9):1183-8
pubmed: 2276081
Front Syst Neurosci. 2014 Dec 10;8:236
pubmed: 25540613
Cell Mol Neurobiol. 1993 Aug;13(4):433-55
pubmed: 8252612
Compr Physiol. 2015 Jul 1;5(3):1161-82
pubmed: 26140713
Neuroscience. 1990;39(3):579-604
pubmed: 1711170
Annu Rev Med. 1997;48:129-56
pubmed: 9046951
Neuroscience. 2009 Jan 12;158(1):284-92
pubmed: 19000744
Mol Endocrinol. 2013 Oct;27(10):1655-65
pubmed: 23979842
Trends Endocrinol Metab. 2013 Dec;24(12):616-24
pubmed: 24063974
J Neurophysiol. 1998 Apr;79(4):1733-45
pubmed: 9535943
PLoS One. 2016 Aug 11;11(8):e0159513
pubmed: 27513844
Glia. 2015 Jan;63(1):154-62
pubmed: 25130497
J Biol Chem. 2016 Aug 26;291(35):18072-83
pubmed: 27402852
Neuroscience. 2006 Jun 30;140(2):555-65
pubmed: 16626867
Brain Res. 1997 Sep 12;768(1-2):185-96
pubmed: 9369315
Forensic Sci Int. 2004 Dec 16;146(2-3):105-10
pubmed: 15542270