Matrix metalloproteinase-9 is increased in obese subjects and decreases in response to pioglitazone

The study investigated the regulation of matrix metalloproteinases (MMP)-9 in obesity-associated insulin resistance in humans. The objectives of the investigation were to study MMP-9 regulation by insulin resistance and pioglitazone treatment in impaired glucose tolerant subjects using adipose tissu...

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Vydáno v:	The journal of clinical endocrinology and metabolism Ročník 95; číslo 6; s. 2993
Hlavní autoři:	Unal, Resat, Yao-Borengasser, Aiwei, Varma, Vijayalakshmi, Rasouli, Neda, Labbate, Craig, Kern, Philip A, Ranganathan, Gouri
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 01.06.2010
Témata:	Adipocytes - drug effects Adipocytes - enzymology Adipose Tissue - enzymology Adult Aged Blotting, Western Body Mass Index Cells, Cultured Coculture Techniques Female Humans Hypoglycemic Agents - therapeutic use Insulin Resistance Male Matrix Metalloproteinase 9 - biosynthesis Matrix Metalloproteinase 9 - metabolism Matrix Metalloproteinase Inhibitors Middle Aged Obesity - enzymology Oligonucleotides - metabolism Pioglitazone Protein Kinase C-alpha - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA - biosynthesis RNA - genetics Stromal Cells - drug effects Stromal Cells - enzymology Th1 Cells - drug effects Th1 Cells - enzymology Thiazolidinediones - therapeutic use Transfection Young Adult
ISSN:	1945-7197, 1945-7197
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Shrnutí:	The study investigated the regulation of matrix metalloproteinases (MMP)-9 in obesity-associated insulin resistance in humans. 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. 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 C alpha antisense oligomers, and MMP-9 levels were examined. 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. These data indicate that MMP-9 is elevated in insulin resistance and is reduced by pioglitazone.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	1945-7197 1945-7197
DOI:	10.1210/jc.2009-2623