Endocrine Abstracts

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 signalling in insulin-sensitive or insulin-resistant 3T3-L1 adipocytes.

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.

Results: 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 AKT and p38MAPK (phosphorylation form/total form), but significantly decreased the activation of AMPK in insulin-responsive adipocytes.

Conclusion: Adiponectin deficiency suppresses insulin-induced glucose uptake, insulin signalling, and the AMPK pathway only in insulin-responsive 3T3-L1 adipocytes.