L‐ Cysteine Supplementation Increases Adiponectin Synthesis and Secretion by Upregulating Disulfide Bond A‐like Protein in 3T3‐L1 Adipocytes Exposed to High Glucose

Abstract

Adiponectin is an insulin sensitizer and has antidiabetic properties, and its plasma levels are decreased in obesity and type 2 diabetes (D). Disulfide‐bond A oxidoreductase‐like protein (DsbA‐L) plays an important role in the multimerization and secretion of adiponectin. D patients have lower blood levels of L‐cysteine (LC), a precursor of GSH and hydrogen sulfide. This study investigates the hypothesis that L‐cysteine treatments increase DsbA‐L expression levels and thereby can increase adiponectin synthesis and secretion in high glucose‐treated 3T3‐L1 adipocytes. 3T3‐L1 adipocytes were preincubated (2 hours) with and without L‐cysteine (0‐500 µM) and then exposed to HG (25 mM) for 20 hours. DsbA‐L expression was determined by western blotting and total adiponectin assay by ELISA kit. Results (n=3) show that HG‐alone treatment caused reduced expression of DsbA‐L (28%) in cells and secretion of adiponectin (19.5%) in the medium; and pretreatment with LC increased the level of DsbA‐L expression (18%) and adiponectin secretion (11.5%) in high glucose treated adipocytes. This study suggests that L‐cysteine supplementation upregulate the DsbA‐L and adiponectin synthesis and secretion and thereby can help promote the insulin sensitivity in type 2 diabetic patients. Supported by grant from the NIH/NCCAM (1 R01AT007442).