title: Relationships among protein tyrosine phosphatase 1B, angiotensin II, and insulin-mediated aortic responses in type 2 diabetic Goto-Kakizaki rats.
abstract: OBJECTIVE
  We investigated the relationships among protein tyrosine phosphatase 1B (PTP1B), angiotensin II (Ang II), and insulin signaling in the presence of endothelial dysfunction in type 2 diabetic Goto-Kakizaki (GK) rat aortas.
  
  
  RESULTS
  Aortas isolated from GK or control Wistar rats were examined in the presence or absence of Ang II with or without a selective antagonist of the Ang II type 1 (AT1) receptor or a PTP1B inhibitor to evaluate vascular functional and molecular mechanisms, such as insulin-induced relaxation, nitric oxide (NO) production, phosphorylation of insulin receptor substrate (IRS)-1, endothelial NO synthase (eNOS), and phosphorylation, and the subcellular localization of PTP1B. GK aortas exhibited reductions of: 1) insulin-induced relaxation, 2) NO production, 3) Ser(1177)-p-eNOS, and 4) Tyr(612)-p-IRS-1. Pre-incubation with a PTP1B inhibitor normalized these reductions. In Wistar aortas, the four above-mentioned parameters were reduced by Ang II, but were completely inhibited by co-treatment with the PTP1B inhibitor. The membrane expression of PTP1B was greater in GK than in Wistar aortas, and it was increased by Ang II in Wistar rats. The membrane PTP1B expression in the presence of insulin + Ang II was reduced by the PTP1B inhibitor or AT1-receptor antagonist.
  
  
  CONCLUSIONS
  These results suggest that the membrane PTP1B suppressed insulin-mediated aortic relaxation, and this was due to the Ang II-AT1-receptor signaling pathway. The inhibition of PTP1B warrants further investigation as a potential therapeutic target for endothelial dysfunction in type 2 diabetes.
authors: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors: Shingo
authors: S
authors: Nemoto
authors: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors: Takayuki
authors: T
authors: Matsumoto
authors: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors: Kumiko
authors: K
authors: Taguchi
authors: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: tkoba@hoshi.ac.jp.
authors: Tsuneo
authors: T
authors: Kobayashi
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004791:Enzyme Inhibitors; D007328:Insulin; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat
keywords: Angiotensin II; Goto–Kakizaki rat; Insulin; Protein tyrosine phosphatase 1B