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Abstract
Context: The study investigated the regulation of matrix metalloproteinases (MMP)-9 in obesity-associated insulin resistance in humans.
Objectives: The objectives of the investigation were to study MMP-9 regulation by insulin resistance and pioglitazone treatment in impaired glucose tolerant subjects using adipose tissue biopsies and study the mechanism of MMP-9 regulation by pioglitazone in adipocyte cultures.
Research Design: 86 nondiabetic, weight-stable subjects between 21 and 66 yr of age were recruited in a university hospital research center setting. All subjects underwent a sc adipose tissue incisional biopsy from the lower abdominal wall and insulin sensitivity testing using a frequently sampled iv glucose tolerance test. Impaired glucose-tolerant subjects were randomized to receive metformin or pioglitazone for 10 wk. To study the mechanism of MMP-9 regulation in adipocytes, cells were treated with pioglitazone or protein kinase Cα antisense oligomers, and MMP-9 levels were examined.
Results: There was a positive correlation between MMP-9 and body mass index (r = 0.40, P < 0.01) and negative correlation between MMP-9 and insulin sensitivity (r = -0.46, P < 0.001). The improvement in insulin sensitivity from pioglitazone resulted in a 52 ± 0.2% reduction in MMP-9 mRNA. Fractionation of adipose tissue indicated that MMP-9 was mostly in the stromal vascular fraction. Pioglitazone also decreased MMP-9 in 3T3-F442A adipocytes and THP1 macrophages. Coculture of adipocytes with macrophages augmented MMP-9 expression in adipocytes and pioglitazone decreased MMP-9 in both adipocytes and macrophages.
Conclusion: These data indicate that MMP-9 is elevated in insulin resistance and is reduced by pioglitazone. (J Clin Endocrinol Metab 95: 2993–3001, 2010)
Document Type
Article
Publication Date
6-2010
Digital Object Identifier (DOI)
10.1210/jc.2009-2623
Repository Citation
Unal, Resat; Yao-Borengasser, Aiwei; Varma, Vijayalakshmi; Rasouli, Neda; Labbate, Craig; Kern, Philip A.; and Ranganathan, Gouri, "Matrix Metalloproteinase-9 Is Increased in Obese Subjects and Decreases in Response to Pioglitazone" (2010). Clinical and Translational Science Faculty Publications. 32.
https://uknowledge.uky.edu/ccts_facpub/32
