PMID- 17537841
OWN - NLM
STAT- MEDLINE
DCOM- 20071010
LR  - 20211203
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 293
IP  - 2
DP  - 2007 Aug
TI  - Hyperglycemia impairs glucose and insulin regulation of nitric oxide production 
      in glucose-inhibited neurons in the ventromedial hypothalamus.
PG  - R592-600
AB  - Physiological changes in extracellular glucose, insulin, and leptin regulate 
      glucose-excited (GE) and glucose-inhibited (GI) neurons in the ventromedial 
      hypothalamus (VMH). Nitric oxide (NO) signaling, which is involved in the 
      regulation of food intake and insulin signaling, is altered in obesity and 
      diabetes. We previously showed that glucose and leptin inhibit NO production via 
      the AMP-activated protein kinase (AMPK) pathway, while insulin stimulates NO 
      production via the phosphatidylinositol-3-OH kinase (PI3K) pathway in VMH GI 
      neurons. Hyperglycemia-induced inhibition of AMPK reduces PI3K signaling by 
      activating the mammalian target of rapamycin (mTOR). We hypothesize that 
      hyperglycemia impairs glucose and insulin-regulated NO production in VMH GI 
      neurons. This hypothesis was tested in VMH neurons cultured in hyperglycemic 
      conditions or from streptozotocin-induced type 1 diabetic rats using NO- and 
      membrane potential-sensitive dyes. Neither decreased extracellular glucose from 
      2.5 to 0.5 mM, nor 5 nM insulin increased NO production in VMH neurons in either 
      experimental condition. Glucose- and insulin-regulated NO production was restored 
      in the presence of the AMPK activator, 
      5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside or the mTOR inhibitor 
      rapamycin. Finally, decreased glucose and insulin did not alter membrane 
      potential in VMH neurons cultured in hyperglycemic conditions or from 
      streptozotocin-induced rats. These data suggest that hyperglycemia impairs 
      glucose and insulin regulation of NO production through AMPK inhibition. 
      Furthermore, glucose and insulin signaling pathways interact via the mTOR 
      pathway.
FAU - Canabal, Debra D
AU  - Canabal DD
AD  - Department of Pharmacology & Physiology, New Jersey Medical School, 185 S. Orange 
      Ave., PO Box 1709, Newark, NJ 07101-1709, USA.
FAU - Potian, Joseph G
AU  - Potian JG
FAU - Duran, Ricardo G
AU  - Duran RG
FAU - McArdle, Joseph J
AU  - McArdle JJ
FAU - Routh, Vanessa H
AU  - Routh VH
LA  - eng
GR  - DK-55619/DK/NIDDK NIH HHS/United States
GR  - DK-64566/DK/NIDDK NIH HHS/United States
GR  - NS-045979/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070530
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (4-amino-5-methylamino-2',7'-difluorofluorescein diacetate)
RN  - 0 (Blood Glucose)
RN  - 0 (Fluoresceins)
RN  - 0 (Insulin)
RN  - 0 (Multienzyme Complexes)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
CIN - Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R590-1. PMID: 17609313
MH  - AMP-Activated Protein Kinases
MH  - Acute Disease
MH  - Animals
MH  - Blood Glucose/*metabolism
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Experimental/metabolism
MH  - Diabetes Mellitus, Type 1/metabolism
MH  - Female
MH  - Fluoresceins
MH  - Hyperglycemia/*metabolism
MH  - Insulin/*blood
MH  - Male
MH  - Membrane Potentials/physiology
MH  - Multienzyme Complexes/metabolism
MH  - Neurons/cytology/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type I/metabolism
MH  - Phosphorylation
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases
MH  - Ventromedial Hypothalamic Nucleus/cytology/*metabolism
EDAT- 2007/06/01 09:00
MHDA- 2007/10/11 09:00
CRDT- 2007/06/01 09:00
PHST- 2007/06/01 09:00 [pubmed]
PHST- 2007/10/11 09:00 [medline]
PHST- 2007/06/01 09:00 [entrez]
AID - 00207.2007 [pii]
AID - 10.1152/ajpregu.00207.2007 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R592-600. doi: 
      10.1152/ajpregu.00207.2007. Epub 2007 May 30.