© 2000 American Heart Association, Inc.
Molecular Medicine |
Hyperinsulinemia Enhances Transcriptional Activity of Nuclear Factor-
B Induced by Angiotensin II, Hyperglycemia, and Advanced Glycosylation End Products in Vascular Smooth Muscle Cells
From the Department of Medicine and Research Service of the Denver VA Medical Center and University of Colorado Health Sciences Center (I.G., M.L.G., P.W., B.D.), Denver, Colo, and Department of Medicine (M.B.), Albert Einstein College of Medicine, Bronx, NY.
Correspondence to Dr Boris Draznin, VA Medical Center (151), 1055 Clermont St, Denver, CO 80220. E-mail DrazninB{at}Den-res.org\\ © 2000 American Heart Association, Inc.
Abstract—Pathogenesis
of macrovascular complications of diabetes may involve an activation of
the transcription factor nuclear factor-
B (NF-B) by hyperglycemia
and advanced glycosylation end products (AGEs). Activation of NF-B
is believed to be dependent on activation of the Rho family of GTPases.
Although the precise mechanism of the Rho-mediated action is not
completely understood, posttranslational modification of the Rho
proteins by geranylgeranylation is required for their subsequent
activation. We observed that in cultured vascular smooth muscle cells
(VSMCs), insulin stimulated the activity of geranylgeranyltransferase
(GGTase) I and increased the amounts of geranylgeranylated Rho-A from
47% to 60% (P<0.05). GGTI-286, an inhibitor of
GGTase I, blocked both effects of insulin. Increased availability of
prenylated Rho-A significantly augmented the abilities of angiotensin
II (Ang II), hyperglycemia, and AGEs to activate NF-B, as measured
by NF-B response-element luciferase reporter activity.
Preincubations of VSMCs with insulin for 24 hours doubled NF-B
transactivation by Ang II, hyperglycemia, and AGEs. This priming effect
of insulin was completely inhibited by GGTI-286. We demonstrate for the
first time, to our knowledge, that insulin potentiates
NF-B–dependent transcriptional activity induced by hyperglycemia,
AGEs, and Ang II in VSMCs by increasing the activity of GGTase I and
the availability of geranylgeranylated Rho-A.
Key Words: hyperinsulinemia • muscle, smooth, vascular • angiotensin II • nuclear factor-B • hyperglycemia
This article has been cited by other articles:
 |
|
 |
|
  N. Engberding, A. San Martin, A. Martin-Garrido, M. Koga, L. Pounkova, E. Lyons, B. Lassegue, and K. K. Griendling Insulin-Like Growth Factor-1 Receptor Expression Masks the Antiinflammatory and Glucose Uptake Capacity of Insulin in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 408 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Haurani and P. J. Pagano Adventitial fibroblast reactive oxygen species as autacrine and paracrine mediators of remodeling: Bellwether for vascular disease? Cardiovasc Res, September 1, 2007; 75(4): 679 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Cui, B. Tieu, A. Recinos, R. G. Tilton, and A. R. Brasier RhoA Mediates Angiotensin II-Induced Phospho-Ser536 Nuclear Factor {kappa}B/RelA Subunit Exchange on the Interleukin-6 Promoter in VSMCs Circ. Res., September 29, 2006; 99(7): 723 - 730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ohkawara, T. Ishibashi, T. Sakamoto, K. Sugimoto, K. Nagata, K. Yokoyama, N. Sakamoto, M. Kamioka, I. Matsuoka, S. Fukuhara, et al. Thrombin-induced Rapid Geranylgeranylation of RhoA as an Essential Process for RhoA Activation in Endothelial Cells J. Biol. Chem., March 18, 2005; 280(11): 10182 - 10188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. L. Wang, M. L. Goalstone, and B. Draznin Molecular Mechanisms of Insulin Resistance That Impact Cardiovascular Biology Diabetes, November 1, 2004; 53(11): 2735 - 2740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. T. Bloomgarden Inpatient Diabetes Control: Approaches to treatment Diabetes Care, September 1, 2004; 27(9): 2272 - 2277. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Van den Berghe Tight Blood Glucose Control With Insulin in "Real-Life" Intensive Care Mayo Clin. Proc., August 1, 2004; 79(8): 977 - 978. [PDF]
|
|
|
|
 |
|
 M. A. Creager, T. F. Luscher, F. Cosentino, and J. A. Beckman Diabetes and Vascular Disease: Pathophysiology, Clinical Consequences, and Medical Therapy: Part I Circulation, September 23, 2003; 108(12): 1527 - 1532. [Full Text] [PDF]
|
|
|
|
|
|
C. Yan, D. Kim, T. Aizawa, and B. C. Berk Functional Interplay Between Angiotensin II and Nitric Oxide: Cyclic GMP as a Key Mediator Arterioscler Thromb Vasc Biol, January 1, 2003; 23(1): 26 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Vlassara, W. Cai, J. Crandall, T. Goldberg, R. Oberstein, V. Dardaine, M. Peppa, and E. J. Rayfield Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy PNAS, November 26, 2002; 99(24): 15596 - 15601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. V. Ramana, D. Chandra, S. Srivastava, A. Bhatnagar, B. B. Aggarwal, and S. K. Srivastava Aldose Reductase Mediates Mitogenic Signaling in Vascular Smooth Muscle Cells J. Biol. Chem., August 23, 2002; 277(35): 32063 - 32070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Begum, O. A. Sandu, and N. Duddy Negative Regulation of Rho Signaling by Insulin and Its Impact on Actin Cytoskeleton Organization in Vascular Smooth Muscle Cells: Role of Nitric Oxide and Cyclic Guanosine Monophosphate Signaling Pathways Diabetes, July 1, 2002; 51(7): 2256 - 2263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. James, D. Tang, A. Ingram, H. Ly, K. Thai, L. Cai, and J. W. Scholey Flux Through the Hexosamine Pathway Is a Determinant of Nuclear Factor {kappa}B- Dependent Promoter Activation Diabetes, April 1, 2002; 51(4): 1146 - 1156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. A. Sandu, M. Ito, and N. Begum Signal Transduction in Smooth Muscle: Selected Contribution: Insulin utilizes NO/cGMP pathway to activate myosin phosphatase via Rho inhibition in vascular smooth muscle J Appl Physiol, September 1, 2001; 91(3): 1475 - 1482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Schmidt and D. M. Stern Hyperinsulinemia and Vascular Dysfunction: The Role of Nuclear Factor-{kappa}B, Yet Again Circ. Res., October 27, 2000; 87(9): 722 - 724. [Full Text] [PDF]
|
|
|
|
|
|
D. J. Klemm, J. W. Leitner, P. Watson, A. Nesterova, J. E.-B. Reusch, M. L. Goalstone, and B. Draznin Insulin-induced Adipocyte Differentiation. ACTIVATION OF CREB RESCUES ADIPOGENESIS FROM THE ARREST CAUSED BY INHIBITION OF PRENYLATION J. Biol. Chem., July 20, 2001; 276(30): 28430 - 28435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Montagnani, I. Golovchenko, I. Kim, G. Y. Koh, M. L. Goalstone, A. N. Mundhekar, M. Johansen, D. F. Kucik, M. J. Quon, and B. Draznin Inhibition of Phosphatidylinositol 3-Kinase Enhances Mitogenic Actions of Insulin in Endothelial Cells J. Biol. Chem., January 11, 2002; 277(3): 1794 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chappell, J. W. Leitner, S. Solomon, I. Golovchenko, M. L. Goalstone, and B. Draznin Effect of Insulin on Cell Cycle Progression in MCF-7 Breast Cancer Cells. DIRECT AND POTENTIATING INFLUENCE J. Biol. Chem., October 5, 2001; 276(41): 38023 - 38028. [Abstract] [Full Text] [PDF]
|
|