PMID- 11564986
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20190822
IS  - 0263-6352 (Print)
IS  - 0263-6352 (Linking)
VI  - 19
IP  - 9
DP  - 2001 Sep
TI  - Endogenous angiotensin II suppresses insulin signaling in vascular smooth muscle 
      cells from spontaneously hypertensive rats.
PG  - 1651-8
AB  - BACKGROUND: Angiotensin II (Ang II) has been reported to inhibit insulin 
      signaling at multiple levels in vascular smooth muscle cells (VSMC) in vitro. We 
      have demonstrated that VSMC from spontaneously hypertensive rats (SHR) produce 
      Ang II in a homogeneous culture. OBJECTIVE: In the current study, we investigated 
      influences of endogenous Ang II on insulin signaling in VSMC from SHR. DESIGN AND 
      METHODS: Phosphatidylinositol 3-kinase (PI3-kinase) activity, insulin receptor 
      substrate-1 (IRS-1) associated tyrosine phosphorylation, and p85 subunit of 
      PI3-kinase were measured in VSMC from SHR and normotensive Wistar-Kyoto (WKY) 
      rats in the absence and presence of Ang II type 1 receptor antagonist RNH6270 and 
      mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) 
      inhibitor U0126. RESULTS: Insulin treatment increased PI3-kinase activity in VSMC 
      from WKY rats in a dose-dependent manner. In contrast, insulin treatment of VSMC 
      from SHR did not affect PI3-kinase activity. However, co-treatment of VSMC from 
      SHR with RNH6270 and insulin, increased PI3-kinase activity. PI3-kinase activity, 
      IRS-1-associated tyrosine phosphorylation and p85 subunit of PI3-kinase in VSMC 
      from WKY rats decreased in response to treatment with Ang II and returned to 
      control levels upon co-treatment with U0126. Basal levels of PI3-kinase activity, 
      IRS-1-associated tyrosine phosphorylation, and p85 subunit of PI3-kinase were 
      significantly lower in VSMC from SHR than in cells from WKY rats. U0126 treatment 
      of VSMC from SHR significantly increased levels of PI3-kinase activity, 
      IRS-1-associated tyrosine phosphorylation, and p85 subunit of PI3-kinase. 
      CONCLUSION: These results indicate that endogenous Ang II suppresses insulin 
      signaling in VSMC from SHR by activating extracellular signal-regulated kinase. 
      These findings suggest that tissue Ang II may play a role in insulin resistance 
      in hypertension.
FAU - Fukuda, N
AU  - Fukuda N
AD  - Second Department of Internal Medicine, Nihon University School of Medicine, 
      Tokyo 173-8610, Japan. nhukuda@med.nihon-u.ac.jp
FAU - Satoh, C
AU  - Satoh C
FAU - Hu, W Y
AU  - Hu WY
FAU - Nakayama, M
AU  - Nakayama M
FAU - Kishioka, H
AU  - Kishioka H
FAU - Kanmatsuse, K
AU  - Kanmatsuse K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - 0 (Butadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - 0 (Nitriles)
RN  - 0 (U 0126)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Angiotensin II/*physiology
MH  - Animals
MH  - Butadienes/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Hypertension/*physiopathology
MH  - Insulin/pharmacology/*physiology
MH  - Male
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors
MH  - Muscle, Smooth, Vascular/pathology/*physiopathology
MH  - Nitriles/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats
MH  - Rats, Inbred SHR/*physiology
MH  - Rats, Inbred WKY
MH  - Signal Transduction/drug effects/*physiology
EDAT- 2001/09/21 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/09/21 10:00
PHST- 2001/09/21 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/21 10:00 [entrez]
AID - 10.1097/00004872-200109000-00018 [doi]
PST - ppublish
SO  - J Hypertens. 2001 Sep;19(9):1651-8. doi: 10.1097/00004872-200109000-00018.