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B Suppressive and Inhibitor-B Stimulatory Effects of Troglitazone in Obese Patients with Type 2 Diabetes: Evidence of an Antiinflammatory Action?1
Division of Endocrinology, Diabetes, and Metabolism, State University of New York, and Kaleida Health, Buffalo, New York 14209
Address all correspondence and requests for reprints to: Paresh Dandona, M.D., Ph.D., Diabetes-Endocrinology Center of Western New York, 3 Gates Circle, Buffalo, New York 14209. E-mail: pdandona{at}kaleidahealth.org
Abstract
It has been shown recently that troglitazone exerts an
anti-inflammatory effect, in vitro, and in
experimental animals. To test these properties in humans, we
investigated the effect of troglitazone on the
proinflammatory transcription factor nuclear factor-
B and its
inhibitory protein IB in mononuclear cells (MNC) and plasma soluble
intracellular adhesion molecule-1, monocyte chemoattractant
protein-1, plasminogen activator inhibitor-1, and
C-reactive protein. We also examined the effect of
troglitazone on reactive oxygen species generation,
p47phox subunit expression, 9-hydroxyoctadecadienoic acid
(9-HODE), 13-HODE, o-tyrosine, and
m-tyrosine in obese patients with type 2 diabetes. Seven
obese patients with type 2 diabetes were treated with
troglitazone (400 mg/day) for 4 weeks. Blood samples were
obtained at weekly intervals. Nuclear factor-B binding activity in
MNC nuclear extracts was significantly inhibited after
troglitazone treatment at week 1 and continued to be
inhibited up to week 4. On the other hand, IB protein levels
increased significantly after troglitazone treatment at
week 1, and this increase persisted throughout the study. Plasma
monocyte chemoattractant protein-1 and soluble intracellular
adhesion molecule-1 concentrations did not decrease
significantly after troglitazone treatment, although there
was a trend toward inhibition. Reactive oxygen species generation by
polymorphonuclear cells and MNC, p47phox subunit protein
quantities, plasminogen activator inhibitor-1, and C-reactive
protein levels decreased significantly after troglitazone
intake. 13-HODE/linoleic acid and 9-HODE/linoleic acid ratios also
decreased after troglitazone intake. However,
o-tyrosine/phenylalanine and
m-tyrosine/phenylalanine ratios did not change
significantly. These data show that troglitazone has
profound antiinflammatory effects in addition to antioxidant effects in
obese type 2 diabetics; these effects may be relevant to the recently
described beneficial antiatherosclerotic effects of
troglitazone at the vascular level.
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