XOMA 052, an anti‐IL‐1β monoclonal antibody,prevents IL‐1β‐mediated insulin resistance in 3T3‐L1 adipocytes |
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| Authors: | Masahisa Handa Sandra Vanegas Betty A Maddux Nerissa Mendoza Shirley Zhu Ira D Goldfine Amer M Mirza |
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| Institution: | 1. Preclinical Research and Development, XOMA (US) LLC, Berkeley, California, USA;2. Department of Medicine, University of California, San Francisco, San Francisco, California, USA |
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| 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. Design and 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. Results and Conclusion: 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. |
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