Salvianolic acid B improves insulin secretion from interleukin 1β-treated rat pancreatic islets: The role of PI3K-Akt signaling

Document Type : Research Paper

Authors

1 Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

2 Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Abstract

Background and Objective: Oxidative stress induced by proinflammatory cytokines such as IL-1β plays a major role in β-cell destruction in diabetes type 1. Salvianolic acid B (Sal B) is a polyphenolic compound with antioxidant and protective effects. Thus, objective of this study was to assess the protection exerted by Sal B on isolated rat islets exposed to IL-1β and to investigate an underlying mechanism in vitro.
Materials and Methods: Isolation of pancreatic islets was done by using the collagenase digestion method. Isolated rat islets were divided into 6 groups including: 1. control, 2. interleukin-1β treated, 3 and 4. interleukin-1β treated+ Sal B, 5 and 6. interleukin-1β treated+ Sal B+ PKB and PI3K inhibitors. Interleukin-1β (1 U/ml) was used to induce cytotoxicity after pretreatment with two doses of Sal B (50 μM and 100 μM) and application of each inhibitors was before Sal B.
Results: IL-1β significantly decreased insulin secretion from isolated islets. Pretreatment with Sal B ameliorated the effect of IL-1β on glucose stimulated insulin secretion in a concentration dependent manner. Inhibitors of PKB and PI3K both abolished these improving effect of Sal B.
Conclusion: Sal B that has antioxidant, anti inflammatory and anti apoptotic properties, provided resistance to pancreatic β-cell dysfunction from cytokine in part via PI3K/Akt pathway. The findings represent that it is a promising agent for prevention of β-cell dysfunction in type 1 diabetes.

Keywords

References

  1. Eizirik DL, Mandrup-Poulsen T. A choice of death–the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 2001;44(12):2115-33.
  2. Jörns A, Günther A, Hedrich H-J, Wedekind D, Tiedge M, Lenzen S. Immune cell infiltration, cytokine expression, and β-cell apoptosis during the development of type 1 diabetes in the spontaneously diabetic LEW. 1AR1/Ztm-iddm rat. Diabetes 2005;54 (7): 2041-52.
  3. Cnop M, Welsh N, Jonas J-C, Jörns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic β-cell death in Type 1 and Type 2 diabetes many differences, few similarities. Diabetes 2005;54(suppl 2):S97-S107.
  4. Tabatabaie T, Vasquez-Weldon A, Moore DR, Kotake Y. Free Radicals and the pathogenesis of type 1 diabetes β-cell cytokine-mediated free radical generation via cyclooxygenase-2. Diabetes 2003; 52(8): 1994-9.
  5. Malaisse WJ, Malaisse-Lagae F, Sener A, Pipeleers DG. Determinants of the selective toxicity of alloxan to the pancreatic B cell. Proceedings of the National Academy of Sciences 1982;79(3):927-30.
  6. Hosseini A, Baeeri M, Rahimifard M, Navaei-Nigjeh M, Mohammadirad A, Pourkhalili N, et al. Antiapoptotic effects of cerium oxide and yttrium oxide nanoparticles in isolated rat pancreatic islets. Human & Experimental Toxicology 2013;32(5):544-53.
  7. Rabinovitch A, Suarez-Pinzon WL, Strynadka K, Lakey J, Rajotte R. Human pancreatic islet beta-cell destruction by cytokines involves oxygen free radicals and aldehyde production. The Journal of Clinical Endocrinology & Metabolism 1996;81(9):3197-202.
  8. Ho JH-C, Hong C-Y. Salvianolic acids: small compounds with multiple mechanisms for cardiovascular protection. Journal of Biomedical Science 2011;18(1):1.
  9. Zhao G-R, Zhang H-M, Ye T-X, Xiang Z-J, Yuan Y-J, Guo Z-X, et al. Characterization of the radical scavenging and antioxidant activities of danshensu and salvianolic acid B. Food and Chemical Toxicology 2008;46(1):73-81.
  10. Huang M-Q, Zhou C-J, Zhang Y-P, Zhang X-Q, Xu W, Lin J, et al. Salvianolic Acid B Ameliorates Hyperglycemia and Dyslipidemia in db/db Mice through the AMPK Pathway. Cellular Physiology and Biochemistry 2016;40(5):933-43.
  11. Cheng B, Gong H, Li X, Sun Y, Chen H, Zhang X, et al. Salvianolic acid B inhibits the amyloid formation of human islet amyloid polypeptideand protects pancreatic beta‐cells against cytotoxicity. Proteins: Structure, Function, and Bioinformatics 2013;81(4):613-21.
  12. Xun C, Hu Y, Lu M, Wang S, Lv D. Study of effect of salvianolic acid B on motor function recovery in rats with spinal cord injury. BioMed Research International 2014;2014.
  13. Sun L-Q, Zhao J, Zhang TT, Qu L, Wang X, Xue B, et al. Protective effects of Salvianolic acid B on Schwann cells apoptosis induced by high glucose. Neurochemical research 2012;37(5):996-1010.
  14. Raoufi S, Baluchnejadmojarad T, Roghani M, Ghazanfari T, Khojasteh F, Mansouri M. Antidiabetic potential of salvianolic acid B in multiple low-dose streptozotocin-induced diabetes. Pharmaceutical Biology 2015;53(12):1803-9.
  15. Wrede CE, Dickson LM, Lingohr MK, Briaud I, Rhodes CJ. Protein kinase B/Akt prevents fatty acid-induced apoptosis in pancreatic β-cells (INS-1). Journal of Biological Chemistry 2002;277(51):49676-84.
  16. Wang W, Liu Y, Chen Y, Cao C, Xiang Y, Zhang D, et al. Inhibition of Foxo1 mediates protective effects of ghrelin against lipotoxicity in MIN6 pancreatic β-cells. Peptides. 2010;31(2):307-14.
  17. Martinez SC, Tanabe K, Cras-Méneur C, Abumrad NA, Bernal-Mizrachi E, Permutt MA. Inhibition of Foxo1 protects pancreatic islet β-cells against fatty acid and endoplasmic reticulum stress–induced apoptosis. Diabetes 2008;57(4):846-59.
  18. Wang H-W, Mizuta M, Saitoh Y, Noma K, Ueno H, Nakazato M. Glucagon-like peptide–1 and candesartan additively improve glucolipotoxicity in pancreatic β-cells. Metabolism. 2011;60(8):1081-9.
  19. Higa M, Shimabukuro M, Shimajiri Y, Takasu N, Shinjyo T, Inaba T. Protein kinase B/Akt signalling is required for palmitate‐induced β‐cell lipotoxicity. Diabetes, Obesity and Metabolism 2006;8(2):228-33.
  20. Ma Z, Xia H, Cui S, Yu J. Attenuation of renal ischemic reperfusion injury by salvianolic acid B via suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway. Brazilian Journal of Medical and Biological Research 2017;50(6).
  21. Liu C-L, Xie L-X, Li M, Durairajan SSK, Goto S, Huang J-D. Salvianolic acid B inhibits hydrogen peroxide-induced endothelial cell apoptosis through regulating PI3K/Akt signaling. PloS one 2007;2(12):e1321.
  22. Wang M, Sun G-b, Sun X, Wang H-w, Meng X-b, Qin M, et al. Cardioprotective effect of salvianolic acid B against arsenic trioxide-induced injury in cardiac H9c2 cells via the PI3K/Akt signal pathway. Toxicology Letters 2013;216(2):100-7.
  23. Farrokhi B, Rostamkhani F, Zahediasl S, Zardooz H. Effects of acute and chronic psychological stress on isolated islets' insulin release 2012.
  24. Zardooz H, Asl SZ, Naseri MG. Effect of chronic psychological stress on insulin release from rat isolated pancreatic islets. Life Sciences 2006;79(1):57-62.
  25. Sagheb MM, Azarpira N, Mokhtary M, Hosseini SE, Yaghobi R. The effects of Leptin and Adiponectin on Pdx1, Foxm1, and PPARγ Transcription in Rat Islets of Langerhans. Hepatitis Monthly 2013;13(6).
  26. Zhu Q, Shan X, Miao H, Lu Y, Xu J, You N, et al. Acute activation of acid ceramidase affects cytokine‐induced cytotoxicity in rat islet β‐cells. FEBS Letters 2009;583(12):2136-41.
  27. Mathis D, Vence L, Benoist C. β-Cell death during progression to diabetes. Nature 2001;414(6865):792-8.
  28. Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nature Reviews Endocrinology 2009;5(4):219-26.
  29. Donath MY, Böni-Schnetzler M, Ellingsgaard H, Halban PA, Ehses JA. Cytokine production by islets in health and diabetes: cellular origin, regulation and function. Trends in Endocrinology & Metabolism 2010;21(5):261-7.
  30. Lee J-H, Song M-Y, Song E-K, Kim E-K, Moon WS, Han M-K, et al. Overexpression of SIRT1 protects pancreatic β-cells against cytokine toxicity by suppressing the nuclear factor-κB signaling pathway. Diabetes 2009;58(2):344-51.
  31. Zardooz H, Zahediasl S, Rostamkhani F, Farrokhi B, Nasiraei S, Kazeminezhad B, et al. Effects of acute and chronic psychological stress on isolated islets' insulin release. Excli Journal 2012;11:163.
  32. Sadeghimahalli F, Karbaschi R, Zardooz H, Khodagholi F, Rostamkhani F. Effect of early life stress on pancreatic isolated islets’ insulin secretion in young adult male rats subjected to chronic stress. Endocrine 2015;48(2):493-503.
  33. Bahadar H, Maqbool F, Mostafalou S, Baeeri M, Rahimifard M, Navaei-Nigjeh M, et al. Assessment of benzene induced oxidative impairment in rat isolated pancreatic islets and effect on insulin secretion. Environmental Toxicology and Pharmacology 2015;39(3):1161-9.
  34. Rajan AS, Aguilar-Bryan L, Nelson DA, Yaney GC, Hsu WH, Kunze DL, et al. Ion channels and insulin secretion. Diabetes Care 1990;13(3):340-63.
  35. Novelli M, Beffy P, Menegazzi M, De Tata V, Martino L, Sgarbossa A, et al. St. John’s wort extract and hyperforin protect rat and human pancreatic islets against cytokine toxicity. Acta Diabetologica 2014;51(1):113-21.
  36. Giannoukakis N, Rudert WA, Ghivizzani SC, Gambotto A, Ricordi C, Trucco M, et al. Adenoviral gene transfer of the interleukin-1 receptor antagonist protein to human islets prevents IL-1beta-induced beta-cell impairment and activation of islet cell apoptosis in vitro. Diabetes 1999;48(9):1730-6.
  37. Rabinovitch A, Suarez-Pinzon WL. Cytokines and their roles in pancreatic islet β-cell destruction and insulin-dependent diabetes mellitus. Biochemical Pharmacology 1998;55(8):1139-49.
  38. Li N, Brun T, Cnop M, Cunha DA, Eizirik DL, Maechler P. Transient oxidative stress damages mitochondrial machinery inducing persistent β-cell dysfunction. Journal of Biological Chemistry 2009;284(35):23602-12.
  39. Grankvist K, Marklund SL, Täljedal I. CuZn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase in pancreatic islets and other tissues in the mouse. Biochemical Journal 1981;199(2):393-8.
  40. Dagli Gul AS, Fadillioglu E, Karabulut I, Yesilyurt A, Delibasi T. The effects of oral carvacrol treatment against H2O2 induced injury on isolated pancreas islet cells of rats. Islets 2013;5(4):149-55.
  41. Sumoski W, Baquerizo H, Rabinovitch A. Oxygen free radical scavengers protect rat islet cells from damage by cytokines. Diabetologia 1989;32(11):792-6.
  42. Chen Y-H, Du G-H, Zhang J-T. Salvianolic acid B protects brain against injuries caused by ischemia-reperfusion in rats. Acta Pharmacologica Sinica 2000;21(5):463-6.
  43. Chen H-m, Luo H, Zeng W-b, Liu B, Huang J-c, Liu M, et al. Salvianolic acid B attenuates oxidized low-density lipoprotein-induced endothelial cell apoptosis through inhibition of oxidative stress, p53, and caspase-3 pathways. Chinese Journal of Integrative Medicine 2017:1-7.
  44. Yang TL, Lin FY, Chen YH, Chiu JJ, Shiao MS, Tsai CS, et al. Salvianolic acid B inhibits low‐density lipoprotein oxidation and neointimal hyperplasia in endothelium‐denuded hypercholesterolaemic rabbits. Journal of the Science of Food and Agriculture 2011;91(1):134-41.
  45. Gao H-Y, Li G-Y, Lou M-M, Li X-Y, Wei X-Y, Wang J-H. Hepatoprotective effect of matrine salvianolic acid B salt on carbon tetrachloride-induced hepatic fibrosis. Journal of Inflammation 2012;9(1):1.
  46. Chen T, Liu W, Chao X, Zhang L, Qu Y, Huo J, et al. Salvianolic acid B attenuates brain damage and inflammation after traumatic brain injury in mice. Brain Research Bulletin 2011;84(2):163-8.
  47. Yan X, Zhou T, Tao Y, Wang Q, Liu P, Liu C. Salvianolic acid B attenuates hepatocyte apoptosis by regulating mediators in death 
Journal of Basic and Clinical Pathophysiology
Volume 6, Issue 1
February 2018
Pages 49-55

Files

Share

How to cite

Statistics