Back to Search
Start Over
Molecular mechanism of angiotensin II-induced insulin resistance in aortic vascular smooth muscle cells: Roles of Protein Tyrosine Phosphatase-1B
- Source :
- Vascular Pharmacology. 53:160-168
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- Insulin resistance is an underlying mechanism of type 2 diabetes and its vascular complications. Recent evidence suggests that crosstalk between angiotensin II (Ang II) and the insulin signaling in vascular smooth muscle cell (VSMC) may contribute to cellular insulin resistance. We hypothesized that Ang II inhibits the anti-mitogenic pathways while enhancing the mitogenic pathways stimulated by insulin via activation of Protein Tyrosine Phosphatase-1B (PTP-1B) in VSMC. We found that Ang II significantly inhibited insulin-induced phosphorylation of tyrosine 608 of IRS-1 and serine 473 of Akt, a downstream member of anti-mitogenic pathway of insulin. In contrast, Ang II increased the serine phosphorylation of IRS-1 which was not affected by the presence of insulin. Activation of p42/p44 MAPK (a mitogenic pathway) induced by insulin was further enhanced by Ang II. Transfection of VSMC with PTP-1B antisense oligonucleotide markedly reduced the effects of Ang II on insulin signaling. Furthermore, an increase in VSMC growth was attenuated by PTP-1B antisense only in the presence of both Ang II and insulin. Finally, we also showed that Ang II -induced activation of PTP-1B in VSMC was PKA/JAK2 dependent. We conclude that Ang II modulates both anti-mitogenic and mitogenic pathways of insulin via the activation of PTP-1B.
- Subjects :
- Male
medicine.medical_specialty
Vascular smooth muscle
Physiology
medicine.medical_treatment
Myocytes, Smooth Muscle
Biology
environment and public health
Article
Rats, Sprague-Dawley
Insulin resistance
Internal medicine
Insulin receptor substrate
medicine
Animals
Insulin
Phosphorylation
Protein kinase B
Aorta
Cells, Cultured
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Pharmacology
Angiotensin II
medicine.disease
Rats
Enzyme Activation
enzymes and coenzymes (carbohydrates)
Insulin receptor
Endocrinology
cardiovascular system
biology.protein
Molecular Medicine
Insulin Resistance
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Subjects
Details
- ISSN :
- 15371891
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Vascular Pharmacology
- Accession number :
- edsair.doi.dedup.....00b320d807a8810837a3827cd4f6c8ea
- Full Text :
- https://doi.org/10.1016/j.vph.2010.06.001