Skip to main content
SpringerLink
Log in

High glucose-induced ROS-accumulation in embryo-larval stages of zebrafish leads to mitochondria-mediated apoptosis

  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

In recent decades, diabetes mellitus has become a major chronic disease threatening human health worldwide, and the age of patients tends to be younger; however, the pathogenesis remains unclear, resulting in many difficulties in its treatment. As an ideal model animal, zebrafish can simulate the processes of human diabetes well. In this study, we successfully established a model of diabetic zebrafish larvae in a previous work. Furthermore, transcriptome analysis was completed, and the results suggested that 10.59% of differentially expressed genes (DEGs) related to the apoptosis pathway need to be considered. Then, glucose-induced developmental toxicity, reactive oxygen species (ROS) accumulation, antioxidant system function, apoptosis and mitochondrial dysfunction were measured in zebrafish larvae. We hope that this study will provide valuable reference information for type 2 juvenile diabetes treatment.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Eid S, Sas KM, Abcouwer SF et al (2019) New insights into the mechanisms of diabetic complications: role of lipids and lipid metabolism. Diabetologia 62:1539–1549

    Article  PubMed  PubMed Central  Google Scholar 

  2. Chait A, Bornfeldt KE (2009) Diabetes and atherosclerosis: is there a role for hyperglycemia? J Lipid Res 50:S335–S339

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Gabbay KH (1975) Hyperglycemia, polyol metabolism, and complications of diabetes mellitus. Annu Rev Med 26:521–536

    Article  CAS  PubMed  Google Scholar 

  4. Zheng Y, Ley SH, Hu FB (2018) Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 14:88–98

    Article  PubMed  Google Scholar 

  5. D’Adamo E, Caprio S (2011) Type 2 diabetes in youth: epidemiology and pathophysiology. Diabetes Care 34:S161–S165

    Article  PubMed  PubMed Central  Google Scholar 

  6. Magliano DJ, Sacre JW, Harding JL, Gregg EW, Zimmet PZ, Shaw JE (2020) Young-onset type 2 diabetes mellitus—implications for morbidity and mortality. Nat Rev Endocrinol 16:321–331

    Article  PubMed  Google Scholar 

  7. Akash MSH, Rehman K, Chen S (2013) An overview of valuable scientific models for diabetes mellitus. Curr Diabetes Rev 9:286–293

    Article  PubMed  Google Scholar 

  8. Garcia GR, Noyes PD, Tanguay RL (2016) Advancements in zebrafish applications for 21st century toxicology. Pharmacol Ther 161:11–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pardo-Martin C, Chang TY, Koo BK, Gilleland CL, Wasserman SC, Yanik MF (2010) High-throughput in vivo vertebrate screening. Nat Methods 7:634-U646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lai AKW, Lo ACY (2013) Animal models of diabetic retinopathy: summary and comparison. J Diabetes Res 2013:1–29

    Article  Google Scholar 

  11. Wang XB, Zhang JB, He KJ, Wang F, Liu CF (2021) Advances of zebrafish in neurodegenerative disease: from models to drug discovery. Front Pharmacol 12:19

    Google Scholar 

  12. Alestrom P, Holter JL, Nourizadeh-Lillabadi R (2006) Zebrafish in functional genomics and aquatic biomedicine. Trends Biotechnol 24:15–21

    Article  PubMed  CAS  Google Scholar 

  13. Jurczyk A, Roy N, Bajwa R et al (2011) Dynamic glucoregulation and mammalian-like responses to metabolic and developmental disruption in zebrafish. Gen Comp Endocrinol 170:334–345

    Article  CAS  PubMed  Google Scholar 

  14. Malle EK, Zammit NW, Walters SN et al (2015) Nuclear factor κB–inducing kinase activation as a mechanism of pancreatic β cell failure in obesity. J Exp Med 212:1239–1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Capiotti KM, Antonioli R, Kist LW, Bogo MR, Bonan CD, Da Silva RS (2014) Persistent impaired glucose metabolism in a zebrafish hyperglycemia model. Comp Biochem Physiol B-Biochem Mol Biol 171:58–65

    Article  CAS  PubMed  Google Scholar 

  16. Fang L, Liang XF, Zhou Y et al (2014) Programming effects of high-carbohydrate feeding of larvae on adult glucose metabolism in zebrafish, Danio rerio. Br J Nutr 111:808–818

    Article  CAS  PubMed  Google Scholar 

  17. Tan RR, Li YF, Zhang XT et al (2013) Glucose metabolism disorder is a risk factor in ethanol exposure induced malformation in embryonic brain. Food Chem Toxicol 60:238–245

    Article  CAS  PubMed  Google Scholar 

  18. Elo B, Villano CM, Govorko D, White LA (2007) Larval zebrafish as a model for glucose metabolism: expression of phosphoenolpyruvate carboxykinase as a marker for exposure to anti-diabetic compounds. J Mol Endocrinol 38:433–440

    Article  CAS  PubMed  Google Scholar 

  19. Cox AG, Tsomides A, Yimlamai D et al (2018) Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth. Embo J 37:16

    Article  CAS  Google Scholar 

  20. Rees DA, Alcolado JC (2005) Animal models of diabetes mellitus. Diabetic Med 22:359–370

    Article  CAS  PubMed  Google Scholar 

  21. Zang LQ, Maddison LA, Chen WB (2018) Zebrafish as a model for obesity and diabetes. Front Cell Dev Biol 6:13

    Article  Google Scholar 

  22. Kleinert M, Clemmensen C, Hofmann SM et al (2018) Animal models of obesity and diabetes mellitus. Nat Rev Endocrinol 14:140–162

    Article  PubMed  Google Scholar 

  23. Jin Y, Zhang X, Shu L et al (2010) Oxidative stress response and gene expression with atrazine exposure in adult female zebrafish (Danio rerio). Chemosphere 78:846–852

    Article  CAS  PubMed  Google Scholar 

  24. Jiang JH, Lv L, Wu SG et al (2019) Developmental toxicity of kresoxim-methyl during zebrafish (Danio rerio) larval development. Chemosphere 219:517–525

    Article  CAS  PubMed  Google Scholar 

  25. Mitrakou A (2002) Pathogenesis of hyperglycaemia in type 2 diabetes. Diabetes Obes Metab 4:249–254

    Article  CAS  PubMed  Google Scholar 

  26. Madonna R, Gorbe A, Ferdinandy P, De Caterina R (2013) Glucose metabolism, hyperosmotic stress, and reprogramming of somatic cells. Mol Biotechnol 55:169–178

    Article  CAS  PubMed  Google Scholar 

  27. Giorgi C, Danese A, Missiroli S, Patergnani S, Pinton P (2018) Calcium dynamics as a machine for decoding signals. Trends Cell Biol 28:258–273

    Article  CAS  PubMed  Google Scholar 

  28. von Philipsborn P, Stratil JM, Burns J et al (2019) Environmental interventions to reduce the consumption of sugar-sweetened beverages and their effects on health. Cochrane Database of Syst Rev. https://doi.org/10.1002/14651858.CD012292.pub2

    Article  Google Scholar 

  29. Cree-Green M, Triolo TM, Nadeau KJ (2013) Etiology of insulin resistance in youth with type 2 diabetes. Curr Diab Rep 13:81–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Salehpour A, Rezaei M, Khoradmehr A, Tahamtani Y, Tamadon A (2021) Which hyperglycemic model of zebrafish (Danio rerio) suites my type 2 diabetes mellitus research? A scoring system for available methods. Front Cell Dev Biol 9:15

    Article  Google Scholar 

  31. Peng RX, Lin GG, Li JM (2016) Potential pitfalls of CRISPR/Cas9-mediated genome editing. Febs J 283:1218–1231

    Article  CAS  PubMed  Google Scholar 

  32. Gonzalez-Reyes RE, Aliev G, Avila-Rodrigues M, Barreto GE (2016) Alterations in glucose metabolism on cognition: a possible link between diabetes and dementia. Curr Pharm Design 22:812–818

    Article  CAS  Google Scholar 

  33. King GL, Kunisaki M, Nishio Y, Inoguchi T, Shiba T, Xia P (1996) Biochemical and molecular mechanisms in the development of diabetic vascular complications. Diabetes 45:S105–S108

    Article  CAS  PubMed  Google Scholar 

  34. Wang XC, Dong QX, Chen YH et al (2013) Bisphenol A affects axonal growth, musculature and motor behavior in developing zebrafish. Aquat Toxicol 142:104–113

    PubMed  Google Scholar 

  35. Qian L, Zhang J, Chen XG et al (2019) Toxic effects of boscalid in adult zebrafish (Danio rerio) on carbohydrate and lipid metabolism. Environ Pollut 247:775–782

    Article  CAS  PubMed  Google Scholar 

  36. Yang BY, Zhai G, Gong YL et al (2017) Depletion of insulin receptors leads to beta-cell hyperplasia in zebrafish. Sci Bull 62:486–492

    Article  CAS  Google Scholar 

  37. Webb SE, Li WM, Miller AL (2008) Calcium signalling during the cleavage period of zebrafish development. Philos Trans R Soc Lond, B, Biol Sci 363:1363–1369

    Article  Google Scholar 

  38. Webb SE, Miller AL (2006) Ca2+ signaling during vertebrate somitogenesis. Acta Pharmacol Sin 27:781–790

    Article  CAS  PubMed  Google Scholar 

  39. Moreau M, Neant I, Webb SE, Miller AL, Riou JF, Leclerc C (2016) Ca2+ coding and decoding strategies for the specification of neural and renal precursor cells during development. Cell Calcium 59:75–83

    Article  CAS  PubMed  Google Scholar 

  40. Mapanga RF, Essop MF (2016) Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways. Am J Physiol Heart Circ Physiol 310:H153–H173

    Article  PubMed  Google Scholar 

  41. Inzucchi S, Majumdar S (2015) Glycemic targets what is the evidence? Med Clin North Am 99:47–67

    Article  PubMed  Google Scholar 

  42. Bhatt MP, Lim YC, Hwang J, Na S, Kim YM, Ha KS (2013) C-Peptide prevents hyperglycemia-induced endothelial apoptosis through inhibition of reactive oxygen species-mediated transglutaminase 2 activation. Diabetes 62:243–253

    Article  CAS  PubMed  Google Scholar 

  43. Volpe CMO, Villar-Delfino PH, dos Anjos PMF, Nogueira-Machado JA (2018) Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis 9:9

    Article  CAS  Google Scholar 

  44. Koju N, Taleb A, Zhou JF et al (2019) Pharmacological strategies to lower crosstalk between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondria. Biomed Pharmacother 111:1478–1498

    Article  CAS  PubMed  Google Scholar 

  45. Li YQ, Sun D, Xu K, Jin LB, Peng RY (2021) Hydrogen sulfide enhances plant tolerance to waterlogging stress. Plants 10:13

    Google Scholar 

  46. Jia R, Du JL, Cao LP et al (2019) Antioxidative, inflammatory and immune responses in hydrogen peroxide-induced liver injury of tilapia (GIFT, Oreochromis niloticus). Fish Shellfish Immunol 84:894–905

    Article  CAS  PubMed  Google Scholar 

  47. Sinha K, Das J, Pal PB, Sil PC (2013) Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol 87:1157–1180

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research was founded by the Natural Science Foundation of Zhejiang Province (Grant No. LQ20C020003).

Author information

Author notes

  1. Yaoqi Li and Qianqian Chen have contributed equally to this work.

Authors and Affiliations

  1. Biomedicine Collaborative Innovation Center of Zhejiang Province & Institute of Life Sciences, College of Life and Environmental Science, Wenzhou University, Wenzhou, 325035, China

    Yaoqi Li, Qianqian Chen, Yinai Liu, Liuliu Bi, Libo Jin, Ke Xu & Renyi Peng

Authors
  1. Yaoqi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qianqian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yinai Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liuliu Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Libo Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ke Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Renyi Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YL: Investigation, Data curation, Writing-original draft. QC: Investigation, Data curation. YL: Investigation, Formal analysis. LB: Investigation, Formal analysis. LJ: Writing-Review & Editing. KX: Writing-Review & Editing. RP: Conceptualization, Writing-original draft, Writing-Review & Editing, Project administration, Funding acquisition.

Corresponding authors

Correspondence to Libo Jin, Ke Xu or Renyi Peng.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (TIF 146 KB)

Supplementary file2 (XLSX 10 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Chen, Q., Liu, Y. et al. High glucose-induced ROS-accumulation in embryo-larval stages of zebrafish leads to mitochondria-mediated apoptosis. Apoptosis 27, 509–520 (2022). https://doi.org/10.1007/s10495-022-01731-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-022-01731-2

Keywords

Search

Navigation