title: XOMA 052, an anti-IL-1β monoclonal antibody, prevents IL-1β-mediated insulin resistance in 3T3-L1 adipocytes.
abstract: OBJECTIVE
  Interleukin-1β (IL-1β) has recently been implicated as a major cytokine that is involved in the pancreatic islet inflammation of type 2 diabetes mellitus. This inflammation impairs insulin secretion by inducing beta-cell apoptosis. Recent evidence has suggested that in obesity-induced inflammation, IL-1β plays a key role in causing insulin resistance in peripheral tissues.
  
  
  METHODS
  To further investigate the pathophysiological role of IL-1β in causing insulin resistance, the inhibitory effects of IL-1β on several insulin-dependent metabolic processes in vitro has been neutralized by XOMA 052. The role IL-1β plays in insulin resistance in adipose tissue was assessed using differentiated 3T3-L1 adipocytes and several parameters involved in insulin signaling and lipid metabolism were examined.
  
  
  CONCLUSIONS
  IL-1β inhibited insulin-induced activation of Akt phosphorylation, glucose transport, and fatty acid uptake. IL-1β also blocked insulin-mediated downregulation of suppressor of cytokine signaling-3 expression. Co-preincubation of IL-1β with XOMA 052 neutralized nearly all of these inhibitory effects in 3T3-L1 adipocytes. These studies provide evidence, therefore, that IL-1β is a key proinflammatory cytokine that is involved in inducing insulin resistance. These studies also suggest that the monoclonal antibody XOMA 052 may be a possible therapeutic to effectively neutralize cytokine-mediated insulin resistance in adipose tissue.
authors: Preclinical Research and Development, XOMA (US) LLC, Berkeley, California, USA.
authors: Masahisa
authors: M
authors: Handa
authors: Sandra
authors: S
authors: Vanegas
authors: Betty A
authors: BA
authors: Maddux
authors: Nerissa
authors: N
authors: Mendoza
authors: Shirley
authors: S
authors: Zhu
authors: Ira D
authors: ID
authors: Goldfine
authors: Amer M
authors: AM
authors: Mirza
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D015536:Down-Regulation; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D029681:Arabidopsis Proteins; D016207:Cytokines; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D053583:Interleukin-1beta; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051057:Proto-Oncogene Proteins c-akt; D019751:Intramolecular Transferases; C568454:marneral synthase, Arabidopsis; C547697:gevokizumab