PMID- 25185805
OWN - NLM
STAT- MEDLINE
DCOM- 20151019
LR  - 20211203
IS  - 1522-1598 (Electronic)
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 112
IP  - 10
DP  - 2014 Nov 15
TI  - Glucocorticoids attenuate the central sympathoexcitatory actions of insulin.
PG  - 2597-604
LID - 10.1152/jn.00514.2014 [doi]
AB  - Insulin acts within the central nervous system to regulate food intake and 
      sympathetic nerve activity (SNA). Strong evidence indicates that glucocorticoids 
      impair insulin-mediated glucose uptake and food intake. However, few data are 
      available regarding whether glucocorticoids also modulate the sympathoexcitatory 
      response to insulin. Therefore, the present study first confirmed that chronic 
      administration of glucocorticoids attenuated insulin-induced increases in SNA and 
      then investigated whether these effects were attributed to deficits in central 
      insulin-mediated responses. Male Sprague-Dawley rats were given access to water 
      or a drinking solution of the glucocorticoid agonist dexamethasone (0.3 mug/ml) 
      for 7 days. A hyperinsulinemic-euglycemic clamp significantly increased lumbar 
      SNA in control rats. This response was significantly attenuated in rats given 
      access to dexamethasone for 7, but not 1, days. Similarly, injection of insulin 
      into the lateral ventricle or locally within the arcuate nucleus (ARC) 
      significantly increased lumbar SNA in control rats but this response was absent 
      in rats given access to dexamethasone. The lack of a sympathetic response to 
      insulin cannot be attributed to a generalized depression of sympathetic function 
      or inactivation of ARC neurons as electrical activation of sciatic afferents or 
      ARC injection of gabazine, respectively, produced similar increases in SNA 
      between control and dexamethasone-treated rats. Western blot analysis indicates 
      insulin produced similar activation of Akt Ser(473) and rpS6 Ser(240/244) in the 
      ventral hypothalamus of control and dexamethasone-treated rats. Collectively, 
      these findings suggest that dexamethasone attenuates the sympathoexcitatory 
      actions of insulin through a disruption of ARC neuronal function downstream of 
      Akt or mammalian target of rapamycin (mTOR) signaling.
CI  - Copyright (c) 2014 the American Physiological Society.
FAU - Steiner, Jennifer L
AU  - Steiner JL
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State College of 
      Medicine, Hershey, Pennsylvania;
FAU - Bardgett, Megan E
AU  - Bardgett ME
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State College of 
      Medicine, Hershey, Pennsylvania;
FAU - Wolfgang, Lawrence
AU  - Wolfgang L
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State College of 
      Medicine, Hershey, Pennsylvania;
FAU - Lang, Charles H
AU  - Lang CH
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State College of 
      Medicine, Hershey, Pennsylvania;
FAU - Stocker, Sean D
AU  - Stocker SD
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State College of 
      Medicine, Hershey, Pennsylvania; Department of Neural and Behavioral Sciences, 
      Pennsylvania State College of Medicine, Hershey, Pennsylvania 
      sstocker@hmc.psu.edu.
LA  - eng
GR  - R01 HL113270/HL/NHLBI NIH HHS/United States
GR  - HL-113270/HL/NHLBI NIH HHS/United States
GR  - HL-090826/HL/NHLBI NIH HHS/United States
GR  - F32-AA-023422/AA/NIAAA NIH HHS/United States
GR  - R01 HL090826/HL/NHLBI NIH HHS/United States
GR  - F32 AA023422/AA/NIAAA NIH HHS/United States
GR  - GM-38032/GM/NIGMS NIH HHS/United States
GR  - R01 GM038032/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140903
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (GABA Antagonists)
RN  - 0 (Glucocorticoids)
RN  - 0 (Insulin)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Pyridazines)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 99460MG420 (gabazine)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Arcuate Nucleus of Hypothalamus/*drug effects/physiology
MH  - Blood Pressure/drug effects/physiology
MH  - Dexamethasone/*pharmacology
MH  - Electric Stimulation
MH  - GABA Antagonists/pharmacology
MH  - Glucocorticoids/*pharmacology
MH  - Insulin/*metabolism
MH  - Lumbar Vertebrae
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/metabolism
MH  - Neurons, Afferent/*drug effects/physiology
MH  - Pyridazines/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Sciatic Nerve/*drug effects/physiology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC4233268
OTO - NOTNLM
OT  - Akt
OT  - arcuate nucleus
OT  - dexamethasone
OT  - mTOR
OT  - sympathetic nerve activity
EDAT- 2014/09/05 06:00
MHDA- 2015/10/20 06:00
PMCR- 2015/11/15
CRDT- 2014/09/05 06:00
PHST- 2014/09/05 06:00 [entrez]
PHST- 2014/09/05 06:00 [pubmed]
PHST- 2015/10/20 06:00 [medline]
PHST- 2015/11/15 00:00 [pmc-release]
AID - jn.00514.2014 [pii]
AID - JN-00514-2014 [pii]
AID - 10.1152/jn.00514.2014 [doi]
PST - ppublish
SO  - J Neurophysiol. 2014 Nov 15;112(10):2597-604. doi: 10.1152/jn.00514.2014. Epub 
      2014 Sep 3.