title: L-Cysteine supplementation increases adiponectin synthesis and secretion, and GLUT4 and glucose utilization by upregulating disulfide bond A-like protein expression mediated by MCP-1 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) plays 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 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 supplementation significantly (p < 0.05) promoted the secretion of total and HMW adiponectin secretion in HG-treated adipocytes. In addition, LC significantly (p < 0.05) decreased ROS production and MCP-1 secretion in HG-treated cells. We further investigated whether MCP-1 has any role of LC on DsbA-L expression and adiponectin levels in 3T3-L1 cells. Treatment with LC prevented the decrease in DsbA-L, adiponectin, and GLUT-4 expression in 3T3L1 adipocyte cells exposed to MCP-1. Thus, this study demonstrates that DsbA-L and adiponectin upregulation mediates the beneficial effects of LC on glucose utilization by inhibiting MCP-1 secretion in adipocytes and provides a novel mechanism by which LC supplementation can improve insulin sensitivity in diabetes.
authors.affiliation: Departments of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA.
authors.forename: Arunkumar Elumalai
authors.initials: AE
authors.lastname: Achari
authors.affiliation: Departments of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA. sjain@lsuhsc.edu.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000096:biosynthesis*; D000818:Animals; D003545:Cysteine / Q000494:pharmacology*; D004220:Disulfides / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage*; D051379:Mice; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D052242:Adiponectin; D004220:Disulfides; D005947:Glucose; D003545:Cysteine
keywords: Adipocytes; Adiponectin; Diabetes; Disulfide bond A-like protein; L-cysteine