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Adiponectin deletion impairs insulin signaling in insulin-sensitive but not insulin-resistant 3T3-L1 adipocytes
- Adiponectin deletion impairs insulin signaling in insulin-sensitive but not insulin-resistant 3T3-L1 adipocytes
- Chang, Eugene; Choi, Jung Mook; Park, Se Eun; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Park, Cheol-Young
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- LIFE SCIENCES
- 0024-3205; 1879-0631
- vol. 132, pp. 93 - 100
- Adipocytes; Adiponectin; Insulin signaling; Insulin resistance
- PERGAMON-ELSEVIER SCIENCE LTD
- SCI; SCIE; SCOPUS
- Aims: Previous reports have demonstrated that the adipocyte-derived peptide adiponectin is closely associated with insulin resistance due to its insulin-sensitizing and anti-inflammatory properties in peripheral tissues; however the autocrine effects of adiponectin remain elusive. This study investigated regulatory effects of adiponectin on glucose transport and insulin signaling in insulin-sensitive or insulin-resistant 3T3-L1 adipocytes. Main methods: 3T3-L1 fibroblasts were transfected with non-target or adiponectin (ADN) siRNA and differentiated. Chronic treatment with insulin (24 h, 100 nM) was employed to induce insulin resistance in differentiated adipocytes. Insulin-stimulated glucose transport was measured and protein and mRNA levels were assessed by Western blot and RT-PCR. Key findings: Prolonged incubation with insulin significantly reduced insulin-stimulated glucose uptake, suggesting the development of insulin resistance and adiponectin mRNA expression. In this insulin-resistant condition, adiponectin deletion did not alter insulin-stimulated glucose uptake. In insulin-sensitive adipocytes, adiponectin ablation reduced insulin-stimulated glucose uptake, expression of IRS-1 and GLUT4, and GLUT4 translocation to the membrane. Adiponectin knockdown did not affect the activation of Ala and p38MAPK (phosphorylation form/total form), but significantly decreased the activation of AMPK in insulin-responsive adipocytes. Significance: Adiponectin deficiency suppresses insulin-induced glucose uptake, insulin signaling, and the AMPK pathway only in insulin-responsive 3T3-L1 adipocytes. (C) 2015 Elsevier Inc. All rights reserved.
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