Associations between insulin resistance and TNF-[alpha] in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

• Published in: Diabetologia Vol. 50; no. 12; p. 2562
• Main Authors: Plomgaard, P, Nielsen, A R, Fischer, C P, Mortensen, O H, Broholm, C, Penkowa, M, Krogh-Madsen, R, Erikstrup, C, Lindegaard, B, Petersen, A M; W, Taudorf, S, Pedersen, B K
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.12.2007
• Subjects: Body fat; Insulin resistance
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-007-0834-6

Clear evidence exists that TNF-α inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-α in type 2 diabetes. We obtained blood and biopsy samples from skeletal muscle and subcutaneous adipose tissue in patients with type 2 diabetes (n = 96) and healthy controls matched for age, sex and BMI (n = 103). Patients with type 2 diabetes had higher plasma levels of fasting insulin (p < 0.0001) and glucose (p < 0.0001) compared with controls, but there was no difference between groups with regard to fat mass. Plasma levels of TNF-α (p = 0.0009) and soluble TNF receptor 2 (sTNFR2; p = 0.002) were elevated in diabetic patients. Insulin sensitivity was correlated with quartiles of plasma TNF-α after adjustment for age, sex, obesity, WHR, neutrophils, IL-6 and maximum O2 uptake (VO2/kg) in the diabetes group (p < 0.05). The TNF mRNA content of adipose or muscle tissue did not differ between the groups, whereas muscle TNF-α protein content, evaluated by western blotting, was higher in type 2 diabetic patients. Immunohistochemistry revealed more TNF-α protein in type 2 than in type 1 muscle fibres. After adjustment for multiple confounders, plasma TNF-α is associated with insulin resistance. This supports the idea that TNF-α plays a significant role in the pathogenesis of chronic insulin resistance in humans. However, findings on the TNF-α protein levels in plasma and skeletal muscle indicate that measurement of TNF mRNA content in adipose or muscle tissue provides no information with regard to the degree of insulin resistance. [PUBLICATION ABSTRACT]