title: Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4.
abstract: OBJECTIVE
  Abundant evidence has demonstrated that long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Our previous study reveals a significant association between promoter polymorphisms of Th2-derived cytokine interleukin-4 (IL-4) and T2DM, which suggests possible roles of IL-4 in metabolism. In this study, we focused on examining the putative regulation of glucose and lipid metabolism by IL-4.
  
  
  METHODS
  C57BL/6 mice were intraperitoneally injected with either adenovirus containing full-length IL-4 encoding gene (AdIL-4) or recombinant IL-4 for mimicking the status of transient and long-term IL-4 overexpression, respectively, and the effects of the overexpressed IL-4 to glucose/lipid metabolism and insulin sensitivity were subsequently investigated.
  
  
  RESULTS
  Our results reveal that IL-4 improves insulin sensitivity and glucose tolerance through upregulating Akt phosphorylation while attenuating GSK-3β activities. IL-4 is also involved in lipid metabolism by inhibiting lipid accumulation in fat tissues, which lead to decreased weight gain and fat mass.
  
  
  CONCLUSIONS
  Our results suggest that IL-4 regulates glucose and lipid metabolism by promoting insulin sensitivity, glucose tolerance and inhibiting lipid deposits. This study uncovers the novel roles of IL-4 in metabolism and provides new insights in the interaction between cytokines/immune responses, insulin sensitivity and metabolism.
authors: Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Y-H
authors: YH
authors: Chang
authors: K-T
authors: KT
authors: Ho
authors: S-H
authors: SH
authors: Lu
authors: C-N
authors: CN
authors: Huang
authors: M-Y
authors: MY
authors: Shiau
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D005951:Glucose Tolerance Test; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D015847:Interleukin-4 / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D015847:Interleukin-4; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3