Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues - Association with cytokine expression, insulin resistance, and reduction by pioglitazone

被引:301
作者
Di Gregorio, GB
Yao-Borengasser, A
Rasouli, N
Varma, V
Lu, T
Miles, LM
Ranganathan, G
Peterson, CA
McGehee, RE
Kern, PA
机构
[1] Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA
[2] Univ Arkansas Med Sci, Dept Med, Div Endocrinol, Little Rock, AR 72205 USA
[3] Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA
[4] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA
关键词
D O I
10.2337/diabetes.54.8.2305
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To examine the role of adipose-resident macrophages in insulin resistance, we examined the gene expression of CD68, a macrophage marker, along with macrophage chemoattractant protein-1 (MCP-1) in human subcutaneous adipose tissue using real-time RT-PCR. Both CD68 and MCP-1 mRNAs were expressed in human adipose tissue, primarily in the stromal vascular fraction. When measured in the adipose tissue from subjects with normal glucose tolerance, covering a wide range of BMI (21-51 kg/m(2)) and insulin sensitivity (S-I) (0.6-8.0 x 10(-4) min(-1 .) mu U-1 (.) ml(-1)), CD68 mRNA abundance, which correlated with the number of CD68-positive cells by immunohistochemistry, tended to increase with BMI but was not statistically significant. However, there was a significant inverse relation between CD68 mRNA and S-I (r = -0.55, P = 0.02). In addition, there was a strong positive relationship among adipose tissue CD68 mRNA, tumor necrosis factor-alpha (TNF-alpha) secretion in vitro (r = 0.79, P < 0.005), and plasma interleukin-6 (r = 0.67, P < 0.005). To determine whether improving S-I in subjects with impaired glucose tolerance (IGT) was associated with decreased CD68 expression, IGT subjects were treated for 10 weeks with pioglitazone or metformin. Pioglitazone increased S-I by 60% and in the same subjects reduced both CD68 and MCP-1 mRNAs by > 50%. Furthermore, pioglitazone resulted in a reduction in the number of CD68-positive cells in adipose tissue and reduced plasma TNF-alpha. Metformin had no effect on any of these measures. Thus, treatment with pioglitazone reduces expression of CD68 and MCP-1 in adipose tissue, apparently by reducing macrophage numbers, resulting in reduced inflammatory cytokine production and improvement in S-I.
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页码:2305 / 2313
页数:9
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