XOMA 052, an Anti-IL-1[Beta] Monoclonal Antibody, Prevents IL-1[Beta]-Mediated Insulin Resistance in 3T3-L1 Adipocytes

• Published in: Obesity (Silver Spring, Md.) Vol. 21; no. 2; p. 306
• Main Authors: Handa, Masahisa, Vanegas, Sandra, Maddux, Betty A, Mendoza, Nerissa, Zhu, Shirley, Goldfine, Ira D, Mirza, Amer M
• Format: Journal Article
• Language: English
• Published: Silver Spring Blackwell Publishing Ltd 01.02.2013
• Subjects: Fatty acids; Glucose; Insulin; Insulin resistance; Lipids; Obesity
• ISSN: 1930-7381; 1930-739X

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 playsakeyrole in causing insulin resistance in peripheral tissues. 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. 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.