XOMA 052, an anti-IL-1ß monoclonal antibody, prevents IL-1ß-mediated insulin resistance in 3T3-L1 adipocytes.
Obesity (Silver Spring)
; 21(2): 306-9, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23401297
ABSTRACT
OBJECTIVE:
Interleukin-1ß (IL-1ß) 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-1ß plays a key role in causing insulin resistance in peripheral tissues. DESIGN ANDMETHODS:
To further investigate the pathophysiological role of IL-1ß in causing insulin resistance, the inhibitory effects of IL-1ß on several insulin-dependent metabolic processes in vitro has been neutralized by XOMA 052. The role IL-1ß 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 ANDCONCLUSION:
IL-1ß inhibited insulin-induced activation of Akt phosphorylation, glucose transport, and fatty acid uptake. IL-1ß also blocked insulin-mediated downregulation of suppressor of cytokine signaling-3 expression. Co-preincubation of IL-1ß with XOMA 052 neutralized nearly all of these inhibitory effects in 3T3-L1 adipocytes. These studies provide evidence, therefore, that IL-1ß 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Adipócitos
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Interleucina-1beta
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Anticorpos Monoclonais Humanizados
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article