PMID- 16841179
OWN - NLM
STAT- MEDLINE
DCOM- 20070403
LR  - 20200508
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 295
IP  - 1-2
DP  - 2007 Jan
TI  - Possible role of Akt to improve vascular endothelial dysfunction in diabetic and 
      hyperhomocysteinemic rats.
PG  - 65-74
AB  - The study has been designed to investigate the effect of demethylasterroquinone 
      B1 (DAQ B1), an activator of Akt, in diabetes mellitus (DM) and 
      hyperhomocysteinemia (HHcy)-induced vascular endothelial dysfunction. 
      Streptozotocin (55 mg kg(-1), i.v.) and methionine (1.7% w/w, p.o., 4 weeks) were 
      administered to rats to produce DM (serum glucose >140 mg dl(-1)) and HHcy (serum 
      homocysteine >10 microM), respectively. Vascular endothelial dysfunction was 
      assessed using isolated aortic ring preparation, electron microscopy of thoracic 
      aorta and serum concentration of nitrite/nitrate. The expression of messenger RNA 
      for p22phox and eNOS was assessed by reverse transcription-polymerase chain 
      reaction. Serum thiobarbituric acid reactive substances (TBARS) and aortic 
      superoxide anion were estimated to assess oxidative stress. DAQ B1 (5 mg kg(-1), 
      p.o.) or atorvastatin (30 mg kg(-1), p.o.) in diabetic and hyperhomocysteinemic 
      rats significantly reduced serum glucose and homocysteine concentration. DAQ B1 
      or atorvastatin markedly improved acetylcholine-induced endothelium-dependent 
      relaxation, vascular endothelial lining, serum nitrite/nitrate concentration and 
      serum TBARS in diabetic and hyperhomocysteinemic rats. However, this ameliorative 
      effect of DAQ B1 has been prevented by L-NAME (25 mg kg(-1), i.p.), an inhibitor 
      of eNOS. Therefore, it may be concluded that DAQ B1-induced activation of Akt may 
      activate eNOS and consequently reduce oxidative stress to improve vascular 
      endothelial dysfunction.
FAU - Shah, Dhvanit I
AU  - Shah DI
AD  - Department of Pharmaceutical Sciences & Drug Research, Faculty of Medicine, 
      Punjabi University, Patiala, 147002,
FAU - Singh, Manjeet
AU  - Singh M
LA  - eng
GR  - K01 DK085217/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20060714
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Blood Glucose)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Quinones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 11062-77-4 (Superoxides)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (Cyba protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Aorta/drug effects/enzymology/ultrastructure
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Experimental/chemically induced/*enzymology/*physiopathology
MH  - Endothelium, Vascular/*enzymology/*physiopathology/ultrastructure
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/chemically induced/*enzymology/*physiopathology
MH  - Male
MH  - NADPH Oxidases/genetics/metabolism
MH  - Nitrates/blood
MH  - Nitric Oxide Synthase Type III/genetics/metabolism
MH  - Nitrites/blood
MH  - Proto-Oncogene Proteins c-akt/agonists/*metabolism
MH  - Quinones/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Superoxides/metabolism
MH  - Thiobarbituric Acid Reactive Substances/analysis
MH  - Vasodilation/drug effects
EDAT- 2006/07/15 09:00
MHDA- 2007/04/04 09:00
CRDT- 2006/07/15 09:00
PHST- 2006/03/27 00:00 [received]
PHST- 2006/06/26 00:00 [accepted]
PHST- 2006/07/15 09:00 [pubmed]
PHST- 2007/04/04 09:00 [medline]
PHST- 2006/07/15 09:00 [entrez]
AID - 10.1007/s11010-006-9273-9 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2007 Jan;295(1-2):65-74. doi: 10.1007/s11010-006-9273-9. Epub 
      2006 Jul 14.