title: Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle.
abstract: OBJECTIVE
  Insulin resistance is a major characteristic of type 2 diabetes and is causally associated with obesity. Inflammation plays an important role in obesity-associated insulin resistance, but the underlying mechanism remains unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine with lower circulating levels in obese subjects, and acute treatment with IL-10 prevents lipid-induced insulin resistance. We examined the role of IL-10 in glucose homeostasis using transgenic mice with muscle-specific overexpression of IL-10 (MCK-IL10).
  
  
  METHODS
  MCK-IL10 and wild-type mice were fed a high-fat diet (HFD) for 3 weeks, and insulin sensitivity was determined using hyperinsulinemic-euglycemic clamps in conscious mice. Biochemical and molecular analyses were performed in muscle to assess glucose metabolism, insulin signaling, and inflammatory responses.
  
  
  RESULTS
  MCK-IL10 mice developed with no obvious anomaly and showed increased whole-body insulin sensitivity. After 3 weeks of HFD, MCK-IL10 mice developed comparable obesity to wild-type littermates but remained insulin sensitive in skeletal muscle. This was mostly due to significant increases in glucose metabolism, insulin receptor substrate-1, and Akt activity in muscle. HFD increased macrophage-specific CD68 and F4/80 levels in wild-type muscle that was associated with marked increases in tumor necrosis factor-alpha, IL-6, and C-C motif chemokine receptor-2 levels. In contrast, MCK-IL10 mice were protected from diet-induced inflammatory response in muscle.
  
  
  CONCLUSIONS
  These results demonstrate that IL-10 increases insulin sensitivity and protects skeletal muscle from obesity-associated macrophage infiltration, increases in inflammatory cytokines, and their deleterious effects on insulin signaling and glucose metabolism. Our findings provide novel insights into the role of anti-inflammatory cytokine in the treatment of type 2 diabetes.
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Eun-Gyoung
authors.initials: EG
authors.lastname: Hong
authors.forename: Hwi Jin
authors.initials: HJ
authors.lastname: Ko
authors.forename: You-Ree
authors.initials: YR
authors.lastname: Cho
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Zhexi
authors.initials: Z
authors.lastname: Ma
authors.forename: Tim Y
authors.initials: TY
authors.lastname: Yu
authors.forename: Randall H
authors.initials: RH
authors.lastname: Friedline
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kurt-Jones
authors.forename: Robert
authors.initials: R
authors.lastname: Finberg
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Fischer
authors.forename: Erica L
authors.initials: EL
authors.lastname: Granger
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Norbury
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hauschka
authors.forename: William M
authors.initials: WM
authors.lastname: Philbrick
authors.forename: Chun-Geun
authors.initials: CG
authors.lastname: Lee
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D004041:Dietary Fats / Q000494:pharmacology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D007328:Insulin; D016753:Interleukin-10; D003402:Creatine Kinase
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