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Effect of Lactobacillus delbrueckii Subsp. lactis PTCC1057 on Serum Glucose, Fetuin-A ,and Sestrin 3 Levels in Streptozotocin-Induced Diabetic Mice

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Abstract

Intake of probiotic bacteria may improve or preserve insulin sensitivity. Fetuin-A and sestrin 3 have emerged as promising candidate biomarkers for crucial roles in insulin signaling pathway. Therefore, the effect of oral supplementation with the probiotic bacterium Lactobacillus delbrueckii subsp. lactis PTCC1057 on proteins involved in insulin signaling pathway was investigated in normal and streptozotocin (STZ)-induced diabetic mice. The 6–8-week-old female mice were divided into a non-diabetic control, diabetic control, and diabetic experimental and non-diabetic experimental groups (5 mice each group). Diabetic and non-diabetic experimental groups treated with 3 × 107 CFU mL−1 L. delbrueckii subsp. lactis PTCC1057 by gavage feeding approach daily for 28 days. Serum glucose, fetuin-A, and sestrin 3 levels were measured by standard methods. The result showed that oral administration of L. delbrueckii significantly decreased serum glucose in comparison to diabetic control group (P = 0.01). Serum fetuin-A level was higher in diabetic control group than non-diabetic group and oral administration of L. delbrueckii subsp. lactis PTCC1057 significantly decreased fetuin-A level in diabetic experimental group in comparison with non-diabetic groups (P = 0.001). Sestrin 3 level significantly was lower in diabetic control group than non-diabetic control group (P = 0.03) and it significantly increased in diabetic experimental group in comparison with diabetic control group after intervention of L. delbrueckii subsp. lactis PTCC1057 (P = 0.02). The results show that feeding the STZ-induced diabetic mice with L. delbrueckii subsp. lactis PTCC1057 terminated to decrease in fasting blood glucose and fetuin-A level and increase in serum sestrin 3 level. Therefore, the L. delbrueckii subsp. lactis PTCC1057 can be considered as excellent candidate for future studies on diabetes mellitus.

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References

  1. Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27(5):1047–1053. https://doi.org/10.2337/diacare.27.5.1047

    Article  PubMed  Google Scholar 

  2. Chawla A, Chawla R, Jaggi S (2016) Microvasular and macrovascular complications in diabetes mellitus: distinct or continuum? Indian J Endocrinol Metab 20(4):546. https://doi.org/10.4103/2230-8210.183480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Goldberg IJ (2001) Diabetic dyslipidemia: causes and consequences. Int J Clin Endocrinol Metab 86(3):965–971. https://doi.org/10.1210/jcem.86.3.7304

    Article  CAS  Google Scholar 

  4. Kahn C (1994) Banting lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 43(8):1066–1084. https://doi.org/10.2337/diab.43.8.1066

    Article  CAS  PubMed  Google Scholar 

  5. Mori K, Emoto M, Yokoyama H, Araki T, Teramura M, Koyama H, Shoji T, Inaba M, Nishizawa Y (2006) Association of serum fetuin-a with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care 29(2):468. https://doi.org/10.2337/diacare.29.02.06.dc05-1484

    Article  PubMed  Google Scholar 

  6. Tao R, Xiong X, Liangpunsakul S, Dong XC (2015) Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling. Diabetes 64(4):1211–1223. https://doi.org/10.2337/db14-0539

    Article  CAS  PubMed  Google Scholar 

  7. Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C, del Cañizo-Gómez FJ (2016) Update on the treatment of type 2 diabetes mellitus. World J Diabetes 7(17):354–395. https://doi.org/10.4239/wjd.v7.i17.354

    Article  PubMed  PubMed Central  Google Scholar 

  8. Jain R, Vyas C (1975) Garlic in alloxan-induced diabetic rabbits. Am J Clin Nutr 28(7):684–685. https://doi.org/10.1093/ajcn/28.7.684

    Article  PubMed  Google Scholar 

  9. Toolsee NA, Aruoma OI, Gunness TK, Kowlessur S, Dambala V, Murad F, Googoolye K, Daus D, Indelicato J (2013) Rondeau P (2013) effectiveness of green tea in a randomized human cohort: relevance to diabetes and its complications. Biomed Res Int 2013:1–12. https://doi.org/10.1155/2013/412379

    Article  CAS  Google Scholar 

  10. Fukino Y, Ikeda A, Maruyama K, Aoki N, Okubo T, Iso H (2008) Randomized controlled trial for an effect of green tea-extract powder supplementation on glucose abnormalities. Eur J Clin Nutr 62(8):953–960. https://doi.org/10.1038/sj.ejcn.1602806

    Article  CAS  PubMed  Google Scholar 

  11. Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490(7418):55–60. https://doi.org/10.1038/nature11450

    Article  CAS  PubMed  Google Scholar 

  12. Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, Al-Soud WA, Sørensen SJ, Hansen LH, Jakobsen M (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5(2):e9085. https://doi.org/10.1371/journal.pone.0009085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Karlsson FH, Tremaroli V, Nookaew I, Bergström G, Behre CJ, Fagerberg B, Nielsen J, Bäckhed F (2013) Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498(7452):99–103. https://doi.org/10.1038/nature12198

    Article  CAS  PubMed  Google Scholar 

  14. Sato J, Kanazawa A, Ikeda F, Yoshihara T, Goto H, Abe H, Komiya K, Kawaguchi M, Shimizu T, Ogihara T (2014) Gut dysbiosis and detection of “live gut bacteria” in blood of Japanese patients with type 2 diabetes. Diabetes Care 37(8):2343–2350. https://doi.org/10.2337/dc13-2817

    Article  CAS  PubMed  Google Scholar 

  15. Allin KH, Nielsen T, Pedersen O (2015) Mechanisms in endocrinology: gut microbiota in patients with type 2 diabetes mellitus. Eur J Endocrinol 172(4):R167–R177. https://doi.org/10.1530/EJE-14-0874

    Article  CAS  PubMed  Google Scholar 

  16. Psichas A, Sleeth M, Murphy K, Brooks L, Bewick G, Hanyaloglu A, Ghatei M, Bloom S, Frost G (2015) The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes 39(3):424–429. https://doi.org/10.1038/ijo.2014.153

    Article  CAS  Google Scholar 

  17. Cani PD, Lecourt E, Dewulf EM, Sohet FM, Pachikian BD, Naslain D, De Backer F, Neyrinck AM, Delzenne NM (2009) Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr 90(5):1236–1243. https://doi.org/10.3945/ajcn.2009.28095

    Article  CAS  PubMed  Google Scholar 

  18. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56(7):1761–1772. https://doi.org/10.2337/db06-1491

    Article  CAS  PubMed  Google Scholar 

  19. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S (2014) The international scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11(8):506–514. https://doi.org/10.1038/nrgastro.2014.66

    Article  PubMed  Google Scholar 

  20. Ashraf R, Shah NP (2014) Immune system stimulation by probiotic microorganisms. Crit Rev Food Sci Nutr 54(7):938–956. https://doi.org/10.1080/10408398.2011.619671

    Article  CAS  PubMed  Google Scholar 

  21. Guarino A, Guandalini S, Lo Vecchio A (2015) Probiotics for prevention and treatment of diarrhea. Curr Opin Gastroenterol 49(Suppl 1):S37–S45. https://doi.org/10.1097/mcg.0000000000000349

    Article  CAS  Google Scholar 

  22. Li C, Li X, Han H, Cui H, Peng M, Wang G, Wang Z (2016) Effect of probiotics on metabolic profiles in type 2 diabetes mellitus: a meta-analysis of randomized, controlled trials. Medicine 95(26):e4088. https://doi.org/10.1097/MD.0000000000004088

    Article  PubMed  PubMed Central  Google Scholar 

  23. Madempudi RS, Ahire JJ, Neelamraju J, Tripathi A, Nanal S (2019) Efficacy of UB0316, a multi-strain probiotic formulation in patients with type 2 diabetes mellitus: a double blind, randomized, placebo controlled study. PLoS One 14(11):e0225168. https://doi.org/10.1371/journal.pone.0225168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sudha MR, Ahire JJ, Jayanthi N, Tripathi A, Nanal S (2019) Effect of multi-strain probiotic (UB0316) in weight management in overweight/obese adults: a 12-week double blind, randomised, placebo-controlled study. Benef Microbes 10(8):855–866. https://doi.org/10.3920/bm2019.0052

    Article  CAS  PubMed  Google Scholar 

  25. Reid G, Abrahamsson T, Bailey M, Bindels LB, Bubnov R, Ganguli K, Martoni C, O’Neill C, Savignac HM, Stanton C (2017) How do probiotics and prebiotics function at distant sites? Benef Microbes 8(4):521–533. https://doi.org/10.3920/BM2016.0222

    Article  CAS  PubMed  Google Scholar 

  26. Ruan Y, Sun J, He J, Chen F, Chen R, Chen H (2015) Effect of probiotics on glycemic control: a systematic review and meta-analysis of randomized, controlled trials. PLoS One 10(7):e0132121. https://doi.org/10.1371/journal.pone.0132121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang Q, Wu Y, Fei X (2016) Effect of probiotics on glucose metabolism in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Medicina 52(1):28–34. https://doi.org/10.1016/j.medici.2015.11.008

    Article  CAS  PubMed  Google Scholar 

  28. Bubnov RV, Babenko LP, Lazarenko LM, Mokrozub VV, Demchenko OA, Nechypurenko OV, Spivak MY (2017) Comparative study of probiotic effects of Lactobacillus and Bifidobacteria strains on cholesterol levels, liver morphology and the gut microbiota in obese mice. EPMA J 8(4):357–376. https://doi.org/10.1007/s13167-017-0117-3

    Article  PubMed  PubMed Central  Google Scholar 

  29. Bernardeau M, Guguen M, Vernoux JP (2006) Beneficial lactobacilli in food and feed: long-term use, biodiversity and proposals for specific and realistic safety assessments. FEMS Microbiol Rev 30(4):487–513. https://doi.org/10.1111/j.1574-6976.2006.00020.x

    Article  CAS  PubMed  Google Scholar 

  30. El Kafsi H, Binesse J, Loux V, Buratti J, Boudebbouze S, Dervyn R, Kennedy S, Galleron N, Quinquis B, Batto J-M (2014) Lactobacillus delbrueckii ssp. lactis and ssp. bulgaricus: a chronicle of evolution in action. BMC Genomics 15(1):407. https://doi.org/10.1186/1471-2164-15-407

    Article  PubMed  PubMed Central  Google Scholar 

  31. Larsen MO, Wilken M, Gotfredsen CF, Carr RD, Svendsen O, Rolin B (2002) Mild streptozotocin diabetes in the Gottingen minipig. A novel model of moderate insulin deficiency and diabetes. Am J Physiol Endocrinol Metab 282(6):E1342–E1351. https://doi.org/10.1152/ajpendo.00564.2001

    Article  CAS  PubMed  Google Scholar 

  32. Yao K, Zeng L, He Q, Wang W, Lei J, Zou X (2017) Effect of probiotics on glucose and lipid metabolism in type 2 diabetes mellitus: a meta-analysis of 12 randomized controlled trials. Med Sci Monit 23:3044. https://doi.org/10.12659/msm.902600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sun J, Buys NJ (2016) Glucose-and glycaemic factor-lowering effects of probiotics on diabetes: a meta-analysis of randomised placebo-controlled trials. Br J Nutr 115(7):1167–1177. https://doi.org/10.1017/S0007114516000076

    Article  CAS  PubMed  Google Scholar 

  34. Kasińska MA, Drzewoski J (2015) Effectiveness of probiotics in type 2 diabetes: a meta-analysis. Pol Arch Med Wewn 125(11):803–813. https://doi.org/10.20452/pamw.3156

    Article  PubMed  Google Scholar 

  35. Choi KM, Han KA, Ahn HJ, Lee SY, Hwang SY, Kim BH, Hong HC, Choi HY, Yang SJ, Yoo HJ (2013) The effects of caloric restriction on Fetuin-a and cardiovascular risk factors in rats and humans: a randomized controlled trial. Clin Endocrinol 79(3):356–363. https://doi.org/10.1111/cen.12076

    Article  CAS  Google Scholar 

  36. Ismail NA, Ragab S, El Dayem SMA, ElBaky AA, Salah N, Hamed M, Assal H, Koura H (2012) Fetuin-a levels in obesity: differences in relation to metabolic syndrome and correlation with clinical and laboratory variables. Arch Med Sci 8(5):826–833. https://doi.org/10.5114/aoms.2012.31616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Denecke B, Gräber S, Schäfer C, Heiss A, Wöltje M, Jahnen-Dechent W (2003) Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-a. Biochem J 376(Pt 1):135–145. https://doi.org/10.1042/BJ20030676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Srinivas P, Wagner AS, Reddy LV, Deutsch D, Leon MA, Goustin AS, Grunberger G (1993) Serum alpha 2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level. Mol Endocrinol 7(11):1445–1455. https://doi.org/10.1210/mend.7.11.7906861

    Article  CAS  PubMed  Google Scholar 

  39. Sun Z-L, Xie Q-Y, Guo G-L, Ma K, Huang Y-Y (2014) Serum fetuin-a levels in patients with cardiovascular disease: a meta-analysis. Biomed Res Int 2014:691540–691549. https://doi.org/10.1155/2014/691540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S, Ray S, Majumdar SS, Bhattacharya S (2012) Fetuin-a acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 18(8):1279–1285. https://doi.org/10.1038/nm.2851

    Article  CAS  PubMed  Google Scholar 

  41. Mathews ST, Chellam N, Srinivas PR, Cintron VJ, Leon MA, Goustin AS, Grunberger G (2000) α2-HSG, a specific inhibitor of insulin receptor autophosphorylation, interacts with the insulin receptor. Mol Cell Endocrinol 164(1–2):87–98. https://doi.org/10.1016/s0303-7207(00)00237-9

    Article  CAS  PubMed  Google Scholar 

  42. Roshanzamir F, Miraghajani M, Rouhani M, Mansourian M, Ghiasvand R, Safavi S (2017) The association between circulating fetuin-a levels and type 2 diabetes mellitus risk: systematic review and meta-analysis of observational studies. J Endocrinol Investig 41:33–47. https://doi.org/10.1007/s40618-017-0697-8

    Article  CAS  Google Scholar 

  43. Haukeland JW, Dahl TB, Yndestad A, Gladhaug IP, Løberg EM, Haaland T, Konopski Z, Wium C, Aasheim ET, Johansen OE (2012) Fetuin a in nonalcoholic fatty liver disease: in vivo and in vitro studies. Eur J Endocrinol 166(3):503–510. https://doi.org/10.1530/EJE-11-0864

    Article  CAS  PubMed  Google Scholar 

  44. Khalili L, Alipour B, Jafar-Abadi MA, Faraji I, Hassanalilou T, Abbasi MM, Vaghef-Mehrabany E, Sani MA (2019) The effects of Lactobacillus casei on glycemic response, serum sirtuin1 and fetuin-a levels in patients with type 2 diabetes mellitus: a randomized controlled trial. Iran Biomed J 23(1):68. https://doi.org/10.29252/.23.1.68

    Article  PubMed  PubMed Central  Google Scholar 

  45. Yadav H, Lee J-H, Lloyd J, Walter P, Rane SG (2013) Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J Biol Chem 288(35):25088–25097. https://doi.org/10.1074/jbc.M113.452516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Homayouni-Rad A, Soroush A-R, Khalili L, Norouzi-Panahi L, Kasaie Z, Ejtahed H-S (2017) Diabetes management by probiotics: current knowledge and future perspective. Int J Vitam Nutr Res 1(1):1–13. https://doi.org/10.1024/0300-9831/a000273

    Article  CAS  Google Scholar 

  47. Duca FA, Swartz TD, Sakar Y, Covasa M (2012) Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota. PLoS One 7(6):e39748. https://doi.org/10.1371/journal.pone.0039748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lee JH, Budanov AV, Talukdar S, Park EJ, Park HL, Park H-W, Bandyopadhyay G, Li N, Aghajan M, Jang I (2012) Maintenance of metabolic homeostasis by sestrin 2 and sestrin 3. Cell Metab 16(3):311–321. https://doi.org/10.1016/j.cmet.2012.08.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Morrison A, Chen L, Wang J, Zhang M, Yang H, Ma Y, Budanov A, Lee JH, Karin M, Li J (2014) Sestrin 2 promotes LKB1-mediated AMPK activation in the ischemic heart. FASEB J 14-258814. https://doi.org/10.1096/fj.14-258814

  50. Ro S-H, Xue X, Ramakrishnan SK, Cho C-S, Namkoong S, Jang I, Semple IA, Ho A, Park H-W, Shah YM (2016) Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis. Elife 25(5):e12204. https://doi.org/10.7554/eLife.12204

    Article  CAS  Google Scholar 

  51. Ro SH, Xue X, Ramakrishnan SK, Cho CS, Namkoong S, Jang I, Semple IA, Ho A, Park HW, Shah YM, Lee JH (2016) Tumor suppressive role of sestrin 2 during colitis and colon carcinogenesis. Elife 5:e12204. https://doi.org/10.7554/eLife.12204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Cai W, Andres DA (2014) mTORC2 is required for rit-mediated oxidative stress resistance. PLoS One 9(12):e115602. https://doi.org/10.1371/journal.pone.0115602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The present study was supported by a grant from the Vice-Chancellor for Research, MRGUMS, Maragheh, and Iran.

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Hallajzadeh, J., Eslami, R.D. & Tanomand, A. Effect of Lactobacillus delbrueckii Subsp. lactis PTCC1057 on Serum Glucose, Fetuin-A ,and Sestrin 3 Levels in Streptozotocin-Induced Diabetic Mice. Probiotics & Antimicro. Prot. 13, 383–389 (2021). https://doi.org/10.1007/s12602-020-09693-0

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