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Original Articles |
B and Stimulates IB in Mononuclear Cells in Obese Subjects: Evidence for an Anti-inflammatory Effect?
Division of Endocrinology, Diabetes & Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209
Address all correspondence and requests for reprints to: Paresh Dandona, M.D., Director, Diabetes-Endocrinology Center of WNY, 3 Gates Circle, Buffalo, New York 14209. E-mail: pdandona{at}kaleidahealth.org
Abstract
In view of the fact that insulin resistance is associated with
atherogenesis and that troglitazone, an insulin
sensitizer, has anti-inflammatory effects, which may be potentially
antiatherogenic in the long term, we have now investigated whether
insulin has potential anti-inflammatory effects. We infused 2.0 to 2.5
IU/h in 5% dextrose (100 mL/h) iv into 10 obese subjects for 4 h
followed by 5% dextrose alone for 2 h. The rate of insulin
infusion was varied to maintain glucose concentrations as close to the
baseline as possible. Blood samples were obtained before and at 2, 4,
and 6 h. Subjects were also infused with 5% dextrose without
insulin and with saline on separate occasions. Intranuclear nuclear
factor 
B (NFB) in mononuclear cells fell at 2 and further at
4 h, reverting toward the baseline at 6 h
(P < 0.05). IB increased significantly at
2 h, increasing further at 4 h and remaining elevated at
6 h (P < 0.001). Reactive oxygen species
(ROS) generation by mononuclear cells fell significantly at
2 h and fell further at 4 h; it partially reverted to
baseline at 6 h (P < 0.005).
p47phox subunit, the key protein of nicotinamide adenine
dinucleotide phosphate oxidase also fell at 2 h and 4 h,
reverting toward the baseline at 6 h (P <
0.05). In addition, soluble intercellular adhesion molecule-1
(sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and plasminogen
activator inhibitor-1 (PAI-1) fell significantly following
insulin infusion. Glucose or saline infusions without insulin caused no
alteration in NFB, IB, ROS generation, p47phox
subunit, sICAM-1, MCP-1, or PAI-1.
We conclude that insulin has a potent acute anti-inflammatory effect
including a reduction in intranuclear NFB, an increase in IB, and
decreases in ROS generation, p47phox subunit, plasma
soluble intercellular adhesion molecule-1 (sICAM-1), monocyte
chemoattractant protein-1 (MCP-1), and plasminogen activator
inhibitor-1 (PAI-1. This acute anti-inflammatory effect, if
demonstrated in the long term, may have implications for
atherosclerosis and its complications.
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D. Tripathy, P. Mohanty, S. Dhindsa, T. Syed, H. Ghanim, A. Aljada, and P. Dandona Elevation of Free Fatty Acids Induces Inflammation and Impairs Vascular Reactivity in Healthy Subjects Diabetes, December 1, 2003; 52(12): 2882 - 2887. [Abstract] [Full Text] [PDF]
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H. Urakawa, A. Katsuki, Y. Sumida, E. C. Gabazza, S. Murashima, K. Morioka, N. Maruyama, N. Kitagawa, T. Tanaka, Y. Hori, et al. Oxidative Stress Is Associated with Adiposity and Insulin Resistance in Men J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4673 - 4676. [Abstract] [Full Text] [PDF]
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P. Dandona, V. Kumar, A. Aljada, H. Ghanim, T. Syed, D. Hofmayer, P. Mohanty, D. Tripathy, and R. Garg Angiotensin II Receptor Blocker Valsartan Suppresses Reactive Oxygen Species Generation in Leukocytes, Nuclear Factor-{kappa}B, in Mononuclear Cells of Normal Subjects: Evidence of an Antiinflammatory Action J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4496 - 4501. [Abstract] [Full Text] [PDF]
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M. Tomaszewski, F. J. Charchar, M. Przybycin, L. Crawford, A. M. Wallace, K. Gosek, G. D. Lowe, E. Zukowska-Szczechowska, W. Grzeszczak, N. Sattar, et al. Strikingly Low Circulating CRP Concentrations in Ultramarathon Runners Independent of Markers of Adiposity: How Low Can You Go? Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1640 - 1644. [Abstract] [Full Text] [PDF]
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P. Dandona, A. Aljada, A. Chaudhuri, and A. Bandyopadhyay The Potential Influence of Inflammation and Insulin Resistance on the Pathogenesis and Treatment of Atherosclerosis-Related Complications in Type 2 Diabetes J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2422 - 2429. [Full Text] [PDF]
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C. Ronco, R. Bellomo, G. Lonneman, P. K. Agarwal, R. Kumari, M. G. Netea, J. W. Van der Meer, B. J. Kullberg, R. S. Hotchkiss, and I. E. Karl Sepsis -- Theory and Therapies N. Engl. J. Med., April 17, 2003; 348(16): 1600 - 1602. [Full Text] [PDF]
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Z. T. Bloomgarden American Association of Clinical Endocrinologists (AACE) Consensus Conference on the Insulin Resistance Syndrome: 25-26 August 2002, Washington, DC Diabetes Care, March 1, 2003; 26(3): 933 - 939. [Full Text] [PDF]
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S. Schiekofer, M. Andrassy, J. Chen, G. Rudofsky, J. Schneider, T. Wendt, N. Stefan, P. Humpert, A. Fritsche, M. Stumvoll, et al. Acute Hyperglycemia Causes Intracellular Formation of CML and Activation of ras, p42/44 MAPK, and Nuclear Factor {kappa}B in PBMCs Diabetes, March 1, 2003; 52(3): 621 - 633. [Abstract] [Full Text] [PDF]
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Time2Take on risk -- making the link between insulin resistance and cardiovascular risk: Report of a GSK symposium from Diabetes UK, Glasgow, March 19th 2003 The British Journal of Diabetes & Vascular Disease, March 1, 2003; 3(2_suppl): S1 - S8. [PDF]
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P. Dandona, A. Aljada, and A. Bandyopadhyay The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia Diabetes Care, February 1, 2003; 26(2): 516 - 519. [Full Text] [PDF]
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 L. Ryden and K. Malmberg Who are the enemies? Diabetes mellitus -- a major risk factor for ischaemic myocardial injury: new directions in the management of acute coronary syndromes in the diabetic patient Eur. Heart J. Suppl., November 1, 2002; 4(suppl_G): G21 - G25. [Abstract] [PDF]
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M. Soop, H. Duxbury, A. O Agwunobi, J. M. Gibson, S. J. Hopkins, C. Childs, R. G. Cooper, P. Maycock, R. A. Little, and G. L. Carlson Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1276 - E1285. [Abstract] [Full Text] [PDF]
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I. B. Hirsch, A. Coviello, J. E. Mazuski, J. A. Bailey, M. J. Shapiro, K. C. McCowen, J. A. Maykel, B. R. Bistrian, N. J. Nusbaum, G. van den Berghe, et al. Intensive Insulin Therapy in Critically Ill Patients N. Engl. J. Med., May 16, 2002; 346(20): 1586 - 1588. [Full Text] [PDF]
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