TY - JOUR
T1 - Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes
AU - Plomgaard, P
AU - Nielsen, A R
AU - Fischer, C P
AU - Mortensen, O H
AU - Broholm, C
AU - Penkowa, M
AU - Krogh-Madsen, R
AU - Erikstrup, C
AU - Lindegaard, B
AU - Petersen, A M W
AU - Taudorf, S
AU - Pedersen, B K
PY - 2007/12
Y1 - 2007/12
N2 - AIMS/HYPOTHESIS: Clear evidence exists that TNF-alpha inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-alpha in type 2 diabetes.METHODS: 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).RESULTS: 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-alpha (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-alpha after adjustment for age, sex, obesity, WHR, neutrophils, IL-6 and maximum O(2) 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-alpha protein content, evaluated by western blotting, was higher in type 2 diabetic patients. Immunohistochemistry revealed more TNF-alpha protein in type 2 than in type 1 muscle fibres.CONCLUSIONS/INTERPRETATION: After adjustment for multiple confounders, plasma TNF-alpha is associated with insulin resistance. This supports the idea that TNF-alpha plays a significant role in the pathogenesis of chronic insulin resistance in humans. However, findings on the TNF-alpha 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.
AB - AIMS/HYPOTHESIS: Clear evidence exists that TNF-alpha inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-alpha in type 2 diabetes.METHODS: 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).RESULTS: 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-alpha (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-alpha after adjustment for age, sex, obesity, WHR, neutrophils, IL-6 and maximum O(2) 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-alpha protein content, evaluated by western blotting, was higher in type 2 diabetic patients. Immunohistochemistry revealed more TNF-alpha protein in type 2 than in type 1 muscle fibres.CONCLUSIONS/INTERPRETATION: After adjustment for multiple confounders, plasma TNF-alpha is associated with insulin resistance. This supports the idea that TNF-alpha plays a significant role in the pathogenesis of chronic insulin resistance in humans. However, findings on the TNF-alpha 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.
KW - Adipose Tissue/metabolism
KW - Body Composition/physiology
KW - C-Reactive Protein/analysis
KW - Case-Control Studies
KW - Cross-Sectional Studies
KW - Diabetes Mellitus, Type 2/blood
KW - Female
KW - Humans
KW - Insulin Resistance/physiology
KW - Interleukin-6/blood
KW - Leukocyte Count
KW - Male
KW - Middle Aged
KW - Muscle, Skeletal/metabolism
KW - Neutrophils/metabolism
KW - Receptors, Tumor Necrosis Factor, Type II/genetics
KW - Tumor Necrosis Factor-alpha/blood
U2 - 10.1007/s00125-007-0834-6
DO - 10.1007/s00125-007-0834-6
M3 - Journal article
C2 - 17928988
SN - 0012-186X
VL - 50
SP - 2562
EP - 2571
JO - Diabetologia
JF - Diabetologia
IS - 12
ER -