Association between the A-2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus

The molecular mechanisms of obesity-related insulin resistance are incompletely understood. Macrophages accumulate in adipose tissue of obese individuals. In obesity, monocyte chemoattractant protein-1 (MCP-1), a key chemokine in the process of macrophage accumulation, is overexpressed in adipose ti...

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Bibliographic Details
Published in:Diabetologia 2004-09, Vol.47 (9), p.1574-1580
Main Authors: SIMEONI, E, HOFFMANN, M. M, WINKELMANN, B. R, RUIZ, J, FLEURY, S, BOEHM, B. O, MÄRZ, W, VASSALLI, G
Format: Article
Language:English
Subjects:
Adenine
Adipocytes
Aged
Biological and medical sciences
Body fat
Bone marrow
Cardiology
Cardiovascular disease
Chemokine CCL2 - genetics
Chemokines
Cohort Studies
Cytokines
Diabetes
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - genetics
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinology
Endocrinopathies
Female
Genes
Genomics
Glucose
Glucose - metabolism
Guanine
Homeostasis
Humans
Hyperinsulinism - genetics
Insulin resistance
Insulin Resistance - physiology
Male
Medical sciences
Middle Aged
Obesity
Polymorphism
Polymorphism, Single Nucleotide - genetics
Proteins
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Summary:The molecular mechanisms of obesity-related insulin resistance are incompletely understood. Macrophages accumulate in adipose tissue of obese individuals. In obesity, monocyte chemoattractant protein-1 (MCP-1), a key chemokine in the process of macrophage accumulation, is overexpressed in adipose tissue. MCP-1 is an insulin-responsive gene that continues to respond to exogenous insulin in insulin-resistant adipocytes and mice. MCP-1 decreases insulin-stimulated glucose uptake into adipocytes. The A-2518G polymorphism in the distal regulatory region of MCP-1 may regulate gene expression. The aim of this study was to investigate the impact of this gene polymorphism on insulin resistance. We genotyped the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort ( n=3307). Insulin resistance, estimated by homeostasis model assessment, and Type 2 diabetes were diagnosed in 803 and 635 patients respectively. Univariate analysis revealed that plasma MCP-1 levels were significantly and positively correlated with WHR ( p=0.011), insulin resistance ( p=0.0097) and diabetes ( p
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-004-1494-4