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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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