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Obesity (Silver Spring). 2013 Feb;21(2):306-9. doi: 10.1002/oby.20004.

XOMA 052, an anti-IL-1β monoclonal antibody, prevents IL-1β-mediated insulin resistance in 3T3-L1 adipocytes.

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1
Preclinical Research and Development, XOMA (US) LLC, Berkeley, California, USA.

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.

PMID:
23401297
DOI:
10.1002/oby.20004
[Indexed for MEDLINE]
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