Angiotensin II shifts insulin signaling into vascular remodeling from glucose metabolism in vascular smooth muscle cells

Hirofumi Hitomi, Kumiko Kaifu, Yoshiko Fujita, Tadashi Sofue, Daisuke Nakano, Kumiko Moriwaki, Taiga Hara, Hideyasu Kiyomoto, Masakazu Kohno, Hiroyuki Kobori, Akira Nishiyama

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

BackgroundTo clarify the role of angiotensin II (Ang II) in insulin-induced arteriosclerosis, we examined the effects of Ang II on insulin-induced mitogen-activated protein (MAP) kinase activation and cellular hypertrophy in rat vascular smooth muscle cells (VSMCs).MethodsPhosphorylated MAP kinases were detected with western blot analysis. Cellular hypertrophy and glucose uptake were evaluated from incorporation of 3 H-labeled-leucine and-deoxy-D-glucose, respectively. Cell sizes were measured by Coulter counter.ResultsWhile Ang II (100nmol/l, 18h) augmented cellular hypertrophy by insulin (10nmol/l, 24h), insulin alone did not affect hypertrophy without Ang II pretreatment. Insulin increased p38MAP kinase and c-Jun N-terminal kinase (JNK) phosphorylation; in the presence of Ang II, p38MAP kinase, and JNK were further activated by insulin. Treatment of a p38MAP kinase inhibitor, SB203580 (10νmol/l), and a JNK inhibitor, SP600125 (20νmol/l), abrogated the 3 H-leucine incorporation by insulin in the presence of Ang II. Both the Ang II receptor blocker, RNH-6270 (100nmol/l), and an antioxidant, ebselen (40νmol/l), inhibited vascular cell hypertrophy. Specific depletion of insulin receptor substrate-1 with small interfering RNA increased 3 H-leucine incorporation by insulin (10nmol/l, 24h); pretreatment with Ang II attenuated insulin (10nmol/l, 30min)-induced glucose uptake.ConclusionsAng II attenuates insulin-stimulated glucose uptake and enhances vascular cell hypertrophy via oxidative stress-and MAP kinase-mediated pathways in VSMCs. Ang II may also cause insulin signaling to diverge from glucose metabolism into vascular remodeling, affecting insulin-induced arteriosclerosis in hypertension.

Original languageEnglish
Pages (from-to)1149-1155
Number of pages7
JournalAmerican Journal of Hypertension
Volume24
Issue number10
DOIs
Publication statusPublished - 2011 Oct

Keywords

  • angiotensin II
  • blood pressure
  • hypertension
  • insulin resistance
  • oxidative stress
  • signal transduction
  • vascular smooth muscle cell

ASJC Scopus subject areas

  • Internal Medicine

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