Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle.

摘要: OBJECTIVE Insulin resistance is a major characteristic of type 2 diabetes and causally associated with obesity. Inflammation plays an important role in obesity-associated insulin resistance, but the underlying mechanism remains unclear. Interleukin (IL)-10 anti-inflammatory cytokine lower circulating levels obese subjects, acute treatment IL-10 prevents lipid-induced resistance. We examined glucose homeostasis using transgenic mice muscle-specific overexpression (MCK-IL10). RESEARCH DESIGN AND METHODS MCK-IL10 wild-type were fed high-fat diet (HFD) for 3 weeks, sensitivity was determined hyperinsulinemic-euglycemic clamps conscious mice. Biochemical molecular analyses performed muscle to assess metabolism, signaling, inflammatory responses. RESULTS developed no obvious anomaly showed increased whole-body sensitivity. After weeks HFD, comparable obesity littermates remained sensitive skeletal muscle. This mostly due significant increases receptor substrate-1, Akt activity HFD macrophage-specific CD68 F4/80 that marked tumor necrosis factor-α, IL-6, C-C motif chemokine receptor-2 levels. In contrast, protected from diet-induced response CONCLUSIONS These results demonstrate protects macrophage infiltration, cytokines, their deleterious effects on signaling metabolism. Our findings provide novel insights into diabetes.