In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 95, No. 6 ( 2010-06-01), p. 2993-3001
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 & lt; 0.01) and negative correlation between MMP-9 and insulin sensitivity (r = −0.46, P & lt; 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.
Type of Medium:
Online Resource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/jc.2009-2623
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2010
detail.hit.zdb_id:
2026217-6
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