| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
pathway in aortas from diabetic rats with systemic hyperinsulinemia
1 Physiology and Morphology, Hoshi University, Tokyo, 142-8501, Japan
* To whom correspondence should be addressed. E-mail: kamata{at}hoshi.ac.jp.
We investigated the involvement of angiotensin II and phosphatidylinositol 3-kinase in the enhanced aortic contractile responses induced by the hyperinsulinemia present in chronic insulin-treated type 1 diabetic rats. Plasma angiotensin II levels were elevated in untreated diabetic rats (versus controls), and further increased in insulin-treated diabetics. Aortic contractile responses and systolic blood pressure were each significantly enhanced in chronic insulin-treated diabetics (versus the other groups). These insulin-induced enhancements were largely prevented by co-treatment with either losartan (an angiotensin II type1 receptor antagonist) or enalapril [an angiotensin-converting enzyme (ACE) inhibitor]. Incubating the tissue with LY294002 (phosphatidylinositol 3-kinase inhibitor) diminished the enhancements of contractile responses seen in both angiotensin II-incubated aortas and aortas from chronic insulin-treated diabetic rats. The norepinephrine-stimulated levels of p110
-associated phosphatidylinositol 3-kinase activity and p110 protein expression were each increased in aortas from insulin-treated diabetics (versus control and untreated diabetics), and chronic administration of losartan blunted these increases. In diabetic aortas incubated with a low concentration (inducing ~10% of the maximum contraction) of angiotensin II, or with either norepinephrine or isotonic K+, contractions were significantly larger than in non-incubated diabetic aortas. Norepinephrine-stimulated p110 phosphatidylinositol 3-kinase activity was elevated in diabetic aortas co-incubated with a non-contractile dose of angiotensin II. These results suggest that in insulin-treated type 1 diabetic rats with hyperinsulinemia, chronic angiotensin II type1 receptor blockade blunts the increases in both vascular contractility and blood pressure via a decrease in p110 subunit-associated phosphatidylinositol 3-kinase activity.
This article has been cited by other articles:
|
|
 |
|
  T. Kobayashi, K. Taguchi, S. Nemoto, T. Nogami, T. Matsumoto, and K. Kamata Activation of the PDK-1/Akt/eNOS pathway involved in aortic endothelial function differs between hyperinsulinemic and insulin-deficient diabetic rats Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1767 - H1775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fekete, K. Rosta, L. Wagner, A. Prokai, P. Degrell, E. Ruzicska, E. Vegh, M. Toth, K. Ronai, K. Rusai, et al. Na+,K+-ATPase is modulated by angiotensin II in diabetic rat kidney - another reason for diabetic nephropathy? J. Physiol., November 15, 2008; 586(22): 5337 - 5348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zhuang, Q. Pu, B. Ceacareanu, Y. Chang, M. Dixit, and A. Hassid Chronic insulin treatment amplifies PDGF-induced motility in differentiated aortic smooth muscle cells by suppressing the expression and function of PTP1B Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H163 - H173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. M. Farghaly, I. S. Blagbrough, D. A. Medina-Tato, and M. L. Watson Interleukin 13 Increases Contractility of Murine Tracheal Smooth Muscle by a Phosphoinositide 3-kinase p110{delta}-Dependent Mechanism Mol. Pharmacol., May 1, 2008; 73(5): 1530 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Jackson, D. G. Gillespie, C. Zhu, J. Ren, L. C. Zacharia, and Z. Mi {alpha}2-Adrenoceptors Enhance Angiotensin II-Induced Renal Vasoconstriction: Role for NADPH Oxidase and RhoA Hypertension, March 1, 2008; 51(3): 719 - 726. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
