title: Chronic insulin therapy reduces adipose tissue macrophage content in LDL-receptor-deficient mice.
abstract: OBJECTIVE
  Insulin has anti-inflammatory effects in short-term experiments. However, the effects of chronic insulin administration on inflammation are unknown. We hypothesised that chronic insulin administration would beneficially alter adipose tissue inflammation and several circulating inflammatory markers.
  
  
  METHODS
  We administered two forms of long-acting insulin, insulin glargine (A21Gly,B31Arg,B32Arg human insulin) and insulin detemir (B29Lys[ε-tetradecanoyl],desB30 human insulin), to LDL-receptor-deficient mice. After 8 weeks on a diet that causes obesity, hyperglycaemia, adipose tissue macrophage accumulation and atherosclerosis, the mice received subcutaneous glargine, detemir or NaCl (control) for 12 weeks. Serum amyloid A (SAA) and serum amyloid P (SAP), metabolic variables, adipose tissue macrophages and aortic atherosclerosis were evaluated.
  
  
  RESULTS
  Weight gain was equivalent in all groups. The glycated haemoglobin level fell equivalently in both insulin-treated groups. Plasma cholesterol and triacylglycerol levels, and hepatic triacylglycerol level significantly improved in the glargine compared with the detemir or control groups. Levels of mRNA expression for monocyte chemotactic protein-1 and F4/80, a macrophage marker, in adipose tissue were decreased only in the glargine group (p < 0.05). Visceral adipose tissue macrophage content decreased in both insulin groups (p < 0.05), whereas atherosclerosis decreased only in the glargine group. Circulating SAA and SAP did not decrease in either insulin-treated group, but IL-6 levels fell in the glargine-treated mice.
  
  
  CONCLUSIONS
  While chronic insulin administration did not decrease SAA and SAP, administration of glargine but not detemir insulin improved dyslipidaemia, IL-6 levels and atherosclerosis, and both insulins reduced macrophage accumulation in visceral adipose tissue. Thus, chronic insulin therapy has beneficial tissue effects independent of circulating inflammatory markers in this murine model of diet-induced obesity and diabetes.
authors.affiliation: Diabetes Obesity Center for Excellence, Division of Metabolism, Endocrinology and Nutrition, University of Washington, 815 Mercer Street, Box 358055, Seattle, WA 98109, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yoon
authors.forename: S
authors.initials: S
authors.lastname: Subramanian
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Goodspeed
authors.forename: B
authors.initials: B
authors.lastname: Sullivan
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: K D
authors.initials: KD
authors.lastname: O'Brien
authors.forename: A
authors.initials: A
authors.lastname: Chait
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects*; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D001823:Body Composition / Q000187:drug effects; D007150:Immunohistochemistry; D007328:Insulin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000188:drug therapy; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects
chemical_list: D007328:Insulin; D049528:Insulin, Long-Acting; D011973:Receptors, LDL; D000069036:Insulin Glargine; D000069057:Insulin Detemir