TY - JOUR
T1 - Expression of anti-inflammatory macrophage genes within skeletal muscle correlates with insulin sensitivity in human obesity and type 2 diabetes
AU - Fink, L. N.
AU - Oberbach, A.
AU - Costford, S. R.
AU - Chan, K. L.
AU - Sams, A.
AU - Blüher, M.
AU - Klip, A.
N1 - Funding Information:
Funding Patient analysis and sample collection was supported by Deutsche Forschungsgemeinschaft, Clinical Research group ‘Atherobesity’ (KFO152; BL 833/1-1). Biopsy analysis was carried out at The Hospital for Sick Children, supported by Canadian Institutes of Health Research (CIHR) grant 12601 to A. Klip. L. N. Fink was supported by fellowships from the Carlsberg Foundation and Novo Nordisk. S. R. Costford was supported by a Mitacs fellowship.
PY - 2013/7
Y1 - 2013/7
N2 - Aims/hypothesis: Low-grade systemic inflammation and adipose tissue inflammatory macrophages are frequently detected in patients with obesity and type 2 diabetes. Whether inflammatory macrophages also increase in skeletal muscle of individuals with metabolic disorders remains controversial. Here, we assess whether macrophage polarisation markers in skeletal muscle of humans correlate with insulin sensitivity in obesity and type 2 diabetes. Methods: Skeletal muscle biopsies were obtained from individuals of normal weight and with normal glucose tolerance (NGT), and overweight/obese individuals with or without type 2 diabetes. Insulin sensitivity was determined by euglycaemic-hyperinsulinaemic clamps. Expression of macrophage genes was analysed by quantitative RT-PCR. Results: Gene expression of the inflammatory macrophage phenotype marker cluster of differentiation (CD)11c was higher in muscle of type 2 diabetes patients (p = 0.0069), and correlated with HbA 1c (p = 0.0139, ρ = 0.48) and fasting plasma glucose (p = 0.0284, ρ = 0.43), but not after correction for age. Expression of TGFB1, encoding the anti-inflammatory marker TGF-β1, correlated inversely with HbA 1c (p = 0.0095, ρ = -0.50; p = 0.0484, ρ = -0.50) and fasting plasma glucose (p = 0.0471, ρ = -0.39; p = 0.0374, ρ = -0.52) in two cohorts, as did HbA1c with gene expression of macrophage galactose-binding lectin (MGL) (p = 0.0425, ρ = -0.51). TGFB1 expression was higher in NGT individuals than in individuals with type 2 diabetes (p = 0.0303), and correlated with low fasting plasma insulin (p = 0.0310, ρ = -0.42). In exercised overweight/obese individuals, expression of genes for three anti-inflammatory macrophage markers, MGL (p = 0.0031, ρ = 0.71), CD163 (p = 0.0268, ρ = 0.57) and mannose receptor (p = 0.0125, ρ = 0.63), correlated with high glucose-disposal rate. Conclusions/interpretation: Muscle expression of macrophage genes reveals a link between inflammatory macrophage markers, age and high glycaemia, whereas anti-inflammatory markers correlate with low glycaemia and high glucose-disposal rate.
AB - Aims/hypothesis: Low-grade systemic inflammation and adipose tissue inflammatory macrophages are frequently detected in patients with obesity and type 2 diabetes. Whether inflammatory macrophages also increase in skeletal muscle of individuals with metabolic disorders remains controversial. Here, we assess whether macrophage polarisation markers in skeletal muscle of humans correlate with insulin sensitivity in obesity and type 2 diabetes. Methods: Skeletal muscle biopsies were obtained from individuals of normal weight and with normal glucose tolerance (NGT), and overweight/obese individuals with or without type 2 diabetes. Insulin sensitivity was determined by euglycaemic-hyperinsulinaemic clamps. Expression of macrophage genes was analysed by quantitative RT-PCR. Results: Gene expression of the inflammatory macrophage phenotype marker cluster of differentiation (CD)11c was higher in muscle of type 2 diabetes patients (p = 0.0069), and correlated with HbA 1c (p = 0.0139, ρ = 0.48) and fasting plasma glucose (p = 0.0284, ρ = 0.43), but not after correction for age. Expression of TGFB1, encoding the anti-inflammatory marker TGF-β1, correlated inversely with HbA 1c (p = 0.0095, ρ = -0.50; p = 0.0484, ρ = -0.50) and fasting plasma glucose (p = 0.0471, ρ = -0.39; p = 0.0374, ρ = -0.52) in two cohorts, as did HbA1c with gene expression of macrophage galactose-binding lectin (MGL) (p = 0.0425, ρ = -0.51). TGFB1 expression was higher in NGT individuals than in individuals with type 2 diabetes (p = 0.0303), and correlated with low fasting plasma insulin (p = 0.0310, ρ = -0.42). In exercised overweight/obese individuals, expression of genes for three anti-inflammatory macrophage markers, MGL (p = 0.0031, ρ = 0.71), CD163 (p = 0.0268, ρ = 0.57) and mannose receptor (p = 0.0125, ρ = 0.63), correlated with high glucose-disposal rate. Conclusions/interpretation: Muscle expression of macrophage genes reveals a link between inflammatory macrophage markers, age and high glycaemia, whereas anti-inflammatory markers correlate with low glycaemia and high glucose-disposal rate.
KW - Exercise
KW - Inflammation
KW - Insulin resistance
KW - Macrophage galactose-binding lectin
KW - Macrophage polarisation
KW - Mannose receptor
KW - Muscle insulin action
KW - Type 2 diabetes
UR - https://www.scopus.com/pages/publications/84878833173
U2 - 10.1007/s00125-013-2897-x
DO - 10.1007/s00125-013-2897-x
M3 - Article
C2 - 23595247
AN - SCOPUS:84878833173
SN - 0012-186X
VL - 56
SP - 1623
EP - 1628
JO - Diabetologia
JF - Diabetologia
IS - 7
ER -