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

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2016 Feb 22

PMID 26897632

Citations 6

Authors

Arunkumar Elumalai Achari

Sushil K Jain

Affiliations

Soon will be listed here.

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.

Citing Articles

New insights of DsbA-L in the pathogenesis of metabolic diseases.

Li S, Wan J, Peng Z, Huang Q, He B Mol Cell Biochem. 2024; 479(12):3293-3303.

PMID: 38430301 DOI: 10.1007/s11010-024-04964-8.

Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice.

Xu M, Liu X, Bao P, Wang Y, Zhu X, Liu Y Antioxidants (Basel). 2022; 11(11).

PMID: 36358588 PMC: 9687043. DOI: 10.3390/antiox11112216.

Causal Relationship between Adiponectin and Diabetic Retinopathy: A Mendelian Randomization Study in an Asian Population.

Huang Y, Chang Y, Cheng C, Wu C, Liao W, Tsai F Genes (Basel). 2020; 12(1).

PMID: 33374471 PMC: 7823606. DOI: 10.3390/genes12010017.

Hydrogen sulfide increases glutathione biosynthesis, and glucose uptake and utilisation in CC mouse myotubes.

Parsanathan R, Jain S Free Radic Res. 2018; 52(2):288-303.

PMID: 29378451 PMC: 6181233. DOI: 10.1080/10715762.2018.1431626.

Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction.

Achari A, Jain S Int J Mol Sci. 2017; 18(6).

PMID: 28635626 PMC: 5486142. DOI: 10.3390/ijms18061321.

References

Blouet C, Mariotti F, Azzout-Marniche D, Mathe V, Mikogami T, Tome D . Dietary cysteine alleviates sucrose-induced oxidative stress and insulin resistance. Free Radic Biol Med. 2007; 42(7):1089-97. DOI: 10.1016/j.freeradbiomed.2007.01.006. View

Matsubara M, Maruoka S, Katayose S . Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol. 2002; 147(2):173-80. DOI: 10.1530/eje.0.1470173. View

An Z, Wang H, Song P, Zhang M, Geng X, Zou M . Nicotine-induced activation of AMP-activated protein kinase inhibits fatty acid synthase in 3T3L1 adipocytes: a role for oxidant stress. J Biol Chem. 2007; 282(37):26793-26801. DOI: 10.1074/jbc.M703701200. View

Ho E, Chen G, Bray T . Supplementation of N-acetylcysteine inhibits NFkappaB activation and protects against alloxan-induced diabetes in CD-1 mice. FASEB J. 1999; 13(13):1845-54. View

Hirose H, Kawai T, Yamamoto Y, Taniyama M, Tomita M, Matsubara K . Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes. Metabolism. 2002; 51(3):314-7. DOI: 10.1053/meta.2002.30506. View

Manna P, Gungor N, Mcvie R, Jain S . Decreased cystathionine-γ-lyase (CSE) activity in livers of type 1 diabetic rats and peripheral blood mononuclear cells (PBMC) of type 1 diabetic patients. J Biol Chem. 2014; 289(17):11767-11778. PMC: 4002085. DOI: 10.1074/jbc.M113.524645. View

Fu Z, Gilbert E, Liu D . Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev. 2012; 9(1):25-53. PMC: 3934755. View

Longo P, Artese H, Rabelo M, Kawamoto D, Foz A, Romito G . Serum levels of inflammatory markers in type 2 diabetes patients with chronic periodontitis. J Appl Oral Sci. 2014; 22(2):103-8. PMC: 3956401. DOI: 10.1590/1678-775720130540. View

Rains J, Jain S . Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med. 2010; 50(5):567-75. PMC: 3557825. DOI: 10.1016/j.freeradbiomed.2010.12.006. View

10.

Kim C, Park H, Kawada T, Kim J, Lim D, Hubbard N . Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond). 2006; 30(9):1347-55. DOI: 10.1038/sj.ijo.0803259. View

11.

Haber C, Lam T, Yu Z, Gupta N, Goh T, Bogdanovic E . N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress. Am J Physiol Endocrinol Metab. 2003; 285(4):E744-53. DOI: 10.1152/ajpendo.00355.2002. View

12.

Liu M, Xiang R, Wilk S, Zhang N, Sloane L, Azarnoush K . Fat-specific DsbA-L overexpression promotes adiponectin multimerization and protects mice from diet-induced obesity and insulin resistance. Diabetes. 2012; 61(11):2776-86. PMC: 3478538. DOI: 10.2337/db12-0169. View

13.

Combs T, Berg A, Obici S, Scherer P, Rossetti L . Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest. 2001; 108(12):1875-81. PMC: 209474. DOI: 10.1172/JCI14120. View

14.

Jain S, Bull R, Rains J, Bass P, Levine S, Reddy S . Low levels of hydrogen sulfide in the blood of diabetes patients and streptozotocin-treated rats causes vascular inflammation?. Antioxid Redox Signal. 2010; 12(11):1333-7. PMC: 2935346. DOI: 10.1089/ars.2009.2956. View

15.

Manna P, Jain S . Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies. Metab Syndr Relat Disord. 2015; 13(10):423-44. PMC: 4808277. DOI: 10.1089/met.2015.0095. View

16.

Hotta K, Funahashi T, Bodkin N, Ortmeyer H, Arita Y, Hansen B . Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes. 2001; 50(5):1126-33. DOI: 10.2337/diabetes.50.5.1126. View

17.

Xia Z, Guo Z, Nagareddy P, Yuen V, Yeung E, McNeill J . Antioxidant N-acetylcysteine restores myocardial Mn-SOD activity and attenuates myocardial dysfunction in diabetic rats. Eur J Pharmacol. 2006; 544(1-3):118-25. DOI: 10.1016/j.ejphar.2006.06.033. View

18.

Lin C, Yin M, Hsu C, Lin M . Effect of five cysteine-containing compounds on three lipogenic enzymes in Balb/cA mice consuming a high saturated fat diet. Lipids. 2005; 39(9):843-8. DOI: 10.1007/s11745-004-1305-4. View

19.

Akhavan T, Luhovyy B, Brown P, Cho C, Anderson G . Effect of premeal consumption of whey protein and its hydrolysate on food intake and postmeal glycemia and insulin responses in young adults. Am J Clin Nutr. 2010; 91(4):966-75. DOI: 10.3945/ajcn.2009.28406. View

20.

Iyer S, Accardi C, Ziegler T, Blanco R, Ritzenthaler J, Rojas M . Cysteine redox potential determines pro-inflammatory IL-1beta levels. PLoS One. 2009; 4(3):e5017. PMC: 2657829. DOI: 10.1371/journal.pone.0005017. View