ID | 111490 |
Author |
Nazari, Hossein
The University of Tokushima|Semnan University of Medical Science
Takahashi, Akira
The University of Tokushima
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Mawatari, Kazuaki
The University of Tokushima
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Nakano, Masayuki
The University of Tokushima
Kishi, Kazuhiro
The University of Tokushima
Ebina, Yousuke
The University of Tokushima
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Nakaya, Yutaka
The University of Tokushima
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|
Keywords | insulin
angiotensin II
cytoskeleton
angiotensin receptor blockers
matrix metalloproteinase
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Content Type |
Journal Article
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Description | There is crosstalk in intracellular signaling between Angiotensin II (Ang II) and insulin. We hypothesized that the underlying mechanism might be related to changes in cytoskeleton. In the presence of 100 nM of Ang II, insulin-induced glucose uptake was decreased and insulin-induced actin filament organization was inhibited. PKC inhibitors, including GF 109203x and p38 MAPK inhibitor (SB 203580) neither improved insulin-induced actin reorganization nor glucose uptake. In contrast, the Ang II-induced inhibition of glucose uptake and actin filament disorganization was reversed by 10 μmol ERK 1/2 MAPK inhibitor (PD 98059). Pretreatment of Ang II increased ERK1/2 phosphorylation and inhibited insulin-induced Akt phosphorylation. The effect of Ang II on ERK 1/2 phosphorylation was blocked by Ang II type 1 receptor antagonists, RNH 6270 and PD 98059 but not by SB 203580 or Guanosine-5’-O-(2-ThioDiphosphate), a G-protein inhibitor. We next tested the effect of broad-spectrum matrix metalloproteinase (MMP) inhibitor (GM 6001) on Ang II-inhibition of insulin signaling pathway. GM 6001 did not improve Ang II-induced actin filament disorganization and did not inhibit ERK1/2 phosphorylation. From these data in L6 myotube, we conclude that Ang II negatively regulates the insulin signal not through MMP signaling pathway but specifically through MMP-independent ERK 1/2 activation pathway, providing an alternative molecular mechanism for angiotensin-induced insulin resistance.
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Journal Title |
The Journal of Medical Investigation
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ISSN | 13496867
13431420
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NCID | AA11166929
AA12022913
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Publisher | Faculty of Medicine Tokushima University
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Volume | 54
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Issue | 1-2
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Start Page | 19
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End Page | 27
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Sort Key | 19
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Published Date | 2007-02
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Publisher
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departments |
Medical Sciences
Institute of Advanced Medical Sciences
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