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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Handa, Masahisa Vanegas, Sandra Maddux, Betty A. Mendoza, Nerissa Zhu, Shirley Goldfine, Ira D. Mirza, Amer M. |
| Description | Country affiliation: United States Author Affiliation: Handa M ( Preclinical Research and Development, XOMA (US) LLC, Berkeley, California, USA.) |
| 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 AND METHODS: 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 AND CONCLUSION: 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. |
| File Format | HTM / HTML |
| ISSN | 19307381 |
| Issue Number | 2 |
| Volume Number | 21 |
| e-ISSN | 1930739X |
| Journal | Obesity |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2013-02-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Endocrinology Adipocytes Drug Effects Antibodies, Monoclonal, Humanized Pharmacology Insulin Resistance Interleukin-1beta Metabolism 3t3-l1 Cells Adipose Tissue Animals Apoptosis Arabidopsis Proteins Genetics Cell Differentiation Cytokines Diabetes Mellitus, Type 2 Drug Therapy Down-regulation Inflammation Insulin Secretion Insulin Receptor Substrate Proteins Antagonists & Inhibitors Insulin-secreting Cells Intramolecular Transferases Lipid Metabolism Mice Phosphorylation Proto-oncogene Proteins C-akt Signal Transduction Suppressor Of Cytokine Signaling Proteins Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Nutrition and Dietetics Endocrinology, Diabetes and Metabolism Endocrinology |
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