L‐Cysteine Supplementation Increases Adiponectin Synthesis and Secretion, GLUT4 and Glucose Utilization by upregulating Disulfide Bond A‐Like Protein Mediated by MCP‐1 and TNF‐α Inhibition in 3T3‐L1 Adipocytes Exposed to High Glucose

Abstract

Adiponectin is an anti‐diabetic and anti‐atherogenic adipokine; its plasma levels are decreased in obesity, insulin resistance, and type 2 diabetes. An adiponectin‐interacting protein named disulfide bond A‐like protein (DsbA‐L) play an important role in the assembly of adiponectin This study examined the hypothesis that L‐cysteine (LC) regulates glucose homeostasis through the DsbA‐L upregulation and synthesis and secretion of adiponectin in diabetes. 3T3L1 adipocytes were treated with LC (250 and 500 μM, 2 h) and high glucose (HG, 25 mM, 20 h). Results (n=3) showed that LC supplementation significantly (p < 0.05) upregulated the DsbA‐L, adiponectin and GLUT‐4 protein expression and glucose utilization in HG treated adipocytes. LC treatment along with insulin enhanced glucose utilization compared to either insulin or LC alone in HG treated cells (n=2). LC supplementation significantly (p < 0.05) promoted the secretion of total and HMW adiponectin secretion in HG‐treated adipocytes (n=5). In addition, LC significantly (p < 0.05) decreased ROS production and MCP‐1 and TNF‐α secretion in HG treated cells (n=3). We further investigated whether MCP‐1 and TNF‐α has any role of LC on DsbA‐L expression and adiponectin levels in 3T3‐L1 cells. Treatment with LC prevented the decrease in DsbAL (n=4) adiponectin (n=3) and GLUT‐4 (n=3) expression in 3T3L1 adipocyte cells exposed to MCP‐1 and TNF‐α. Thus, this study demonstrates that DsbA‐L and adiponectin upregulation mediates the beneficial effects of LC on glucose utilization by inhibiting MCP‐1 and TNF‐α secretion in adipocytes and provides a novel mechanism by which LC supplementation can improve insulin sensitivity in diabetes.Support or Funding InformationThe authors are supported by grants from the National Institutes of Health RO1 AT007442 and Malcolm Feist Endowed Chair in Diabetes