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ID 111490
著者
Nazari, Hossein The University of Tokushima|Semnan University of Medical Science
原田, 永勝 The University of Tokushima KAKEN研究者をさがす
Nakano, Masayuki The University of Tokushima
岸, 和弘 The University of Tokushima
キーワード
insulin
angiotensin II
cytoskeleton
angiotensin receptor blockers
matrix metalloproteinase
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
The Journal of Medical Investigation
ISSN
13496867
13431420
cat書誌ID
AA11166929
AA12022913
出版者
Faculty of Medicine Tokushima University
54
1-2
開始ページ
19
終了ページ
27
並び順
19
発行日
2007-02
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系
先端酵素学研究所