Obesity Research Today is a free monthly online journal that collates and summarizes the latest research about Obesity, including details on health, diet, prevention, exercise.

Insulin facilitates monocyte migration: a possible link to tissue inflammation in insulin-resistance.

Kappert K, Meyborg H, Clemenz M, Graf K, Fleck E, Kintscher U, Stawowy P

Center for Cardiovascular Research, Institute of Pharmacology, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Hessische Str. 3-4, D-10115 Berlin, Germany.

Mononuclear cells (MNCs) are the primary cell type involved in the pro-inflammatory state of obesity-linked insulin-resistance, and atherosclerosis. Increased serum levels of MMP-9 are reported in insulin-resistant type 2 diabetic patients. Here we demonstrate insulin facilitating human monocytic THP-1 cell chemotaxis via prolonged Erk1/2-dependent induction of MMP-9. In vivo, significantly increased serum levels of MMP-9 were found in obesity-induced hyperinsulinemic C57BL/J6 mice, which were diminished by treatment with the anti-diabetic PPARgamma-ligand pioglitazone. In line with this, pioglitazone inhibited Erk1/2-phosphorylation and subsequent insulin-dependent MMP-9 synthesis in THP-1 cells. Thus, insulin increases MMP-9 gelatinolytic activity in monocytic cells, which results in accelerated chemotaxis. Hyperinsulinemia is associated with enhanced MMP-9 serum levels, potentially facilitating monocyte migration to and infiltration of adipose tissue and the arterial wall, thereby contributing to the increased cardiovascular risk in obese, hyperinsulinemic patients.

Published 6 December 2007 in Biochem Biophys Res Commun, 365(3): 503-8.
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