Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
September-2021 Volume 24 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2021 Volume 24 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway

  • Authors:
    • Ling Tong
    • Weiliang Li
    • Ying Zhang
    • Fan Zhou
    • Yan Zhao
    • Linlin Zhao
    • Jing Liu
    • Zhirui Song
    • Mengchen Yu
    • Chengrui Zhou
    • Airong Yu
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
  • Article Number: 658
    |
    Published online on: July 15, 2021
       https://doi.org/10.3892/mmr.2021.12297
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

As a calcineurin inhibitor, tacrolimus is commonly used as a first‑line immunosuppressant in organ transplant recipients. Post‑transplantation diabetes mellitus (PTDM) is a common complication following kidney transplantation and is associated with immunosuppressant drugs, such as tacrolimus. PTDM caused by tacrolimus may be related to its influence on insulin secretion and insulin resistance. However, the specific mechanism has not been fully elucidated. The aim of the present study was to investigate whether the PI3K/Akt/mTOR signaling pathway served an important role in the pathogenesis of PTDM induced by tacrolimus. In the present study, the Cell Counting Kit‑8 assay was used to measure the effect of tacrolimus on the viability of Min6 mouse insulinoma cells. The effects of tacrolimus on the insulin secretion and the activity of caspase‑3 of Min6 cells stimulated by glucose exposure were measured by ELISA. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using WST‑8 and thiobarbituric acid assays, respectively. The effects of tacrolimus on the mRNA expression levels of PI3K, Akt and mTOR were detected by reverse transcription‑quantitative PCR (RT‑qPCR), whereas the protein expression levels of PI3K, Akt, mTOR, phosphorylated (p)‑AKT and p‑mTOR in Min6 cells were assessed using western blotting. The present data indicated that, compared with the control group, 5, 25 and 50 ng/ml tacrolimus treatment could inhibit the insulin secretion of Min6 cells stimulated by glucose solution, and 50 ng/ml tacrolimus could notably decrease the stimulation index (P<0.05). Moreover, 50 ng/ml tacrolimus markedly increased the activity of caspase‑3 by 175.1% (P<0.05), it also decreased the SOD activity (P<0.01) and increased MDA levels (P<0.05). The RT‑qPCR results demonstrated that the mRNA expression levels of PI3K, Akt and mTOR were downregulated by 25 and 50 ng/ml tacrolimus (P<0.01). Furthermore, the western blotting results suggested that tacrolimus had no significant effects on the expression levels of total PI3K, Akt and mTOR proteins (P>0.05), but 25 and 50 ng/ml tacrolimus could significantly inhibit the expression levels of p‑Akt and p‑mTOR (P<0.01). In conclusion, tacrolimus decreased the activity and insulin secretion of pancreatic β cells and induced the apoptosis of islet β cells by inhibiting the mRNA expression levels of PI3K, Akt and mTOR and reducing the phosphorylation of Akt and mTOR proteins in the PI3K/Akt/mTOR signaling pathway, which may ultimately lead to the occurrence of diabetes mellitus, and may be considered as one of the specific mechanisms of PTDM caused by tacrolimus.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Gomes MB and Cobas RA: Post-transplant diabetes mellitus. Diabetol Metab Syndr. 1:142009. View Article : Google Scholar : PubMed/NCBI

2 

Jenssen T and Hartmann A: Emerging treatments for post-transplantation diabetes mellitus. Nat Rev Nephrol. 11:465–477. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Cosio FG, Kudva Y, van der Velde M, Larson TS, Textor SC, Griffin MD and Stegall MD: New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation. Kidney Int. 67:2415–2421. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Revanur VK, Jardine AG, Kingsmore DB, Jaques BC, Hamilton DH and Jindal RM: Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation. Clin Transplant. 15:89–94. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Kasiske BL, Snyder JJ, Gilbertson D and Matas AJ: Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 3:178–185. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Chowdhury TA: Post-transplant diabetes mellitus. Clin Med (Lond). 19:392–395. 2019. View Article : Google Scholar : PubMed/NCBI

7 

Bloom RD and Crutchlow MF: New-onset diabetes mellitus in the kidney recipient: Diagnosis and management strategies. Clin J Am Soc Nephrol. 3 (Suppl 2):S38–S48. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Vincenti F, Friman S, Scheuermann E, Rostaing L, Jenssen T, Campistol JM, Uchida K, Pescovitz MD, Marchetti P, Tuncer M, et al: Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am J Transplant. 7:1506–1514. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Chakkera HA, Kudva Y and Kaplan B: Calcineurin inhibitors: Pharmacologic mechanisms impacting both insulin resistance and insulin secretion leading to glucose dysregulation and diabetes mellitus. Clin Pharmacol Ther. 101:114–120. 2017. View Article : Google Scholar : PubMed/NCBI

10 

van Hooff JP, Christiaans MH and van Duijnhoven EM: Tacrolimus and posttransplant diabetes mellitus in renal transplantation. Transplantation. 79:1465–1469. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Caillard S, Eprinchard L, Perrin P, Braun L, Heibel F, Moreau F, Kessler L and Moulin B: Incidence and risk factors of glucose metabolism disorders in kidney transplant recipients: Role of systematic screening by oral glucose tolerance test. Transplantation. 91:757–764. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Ishihara H, Asano T, Tsukuda K, Katagiri H, Inukai K, Anai M, Kikuchi M, Yazaki Y, Miyazaki JI and Oka Y: Pancreatic beta cell line MIN6 exhibits characteristics of glucose metabolism and glucose-stimulated insulin secretion similar to those of normal islets. Diabetologia. 36:1139–1145. 1993. View Article : Google Scholar : PubMed/NCBI

13 

Huang X, Liu G, Guo J and Su Z: The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci. 14:1483–1496. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Engelman JA, Luo J and Cantley LC: The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 7:606–619. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Wullschleger S, Loewith R and Hall MN: TOR signaling in growth and metabolism. Cell. 124:471–484. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Redmon JB, Olson LK, Armstrong MB, Greene MJ and Robertson RP: Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA levels, and insulin secretion in HIT-T15 cells. J Clin Invest. 98:2786–2793. 1996. View Article : Google Scholar : PubMed/NCBI

17 

Johnson JD, Ao Z, Ao P, Li H, Dai LJ, He Z, Tee M, Potter KJ, Klimek AM, Meloche RM, et al: Different effects of FK506, rapamycin, and mycophenolate mofetil on glucose-stimulated insulin release and apoptosis in human islets. Cell Transplant. 18:833–845. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Sakata N, Egawa S, Sumi S and Unno M: Optimization of glucose level to determine the stimulation index of isolated rat islets. Pancreas. 36:417–423. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Prokai A, Fekete A, Pasti K, Rusai K, Banki NF, Reusz G and Szabo AJ: The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus. Pediatr Diabetes. 13:81–91. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Rangel EB: Tacrolimus in pancreas transplant: A focus on toxicity, diabetogenic effect and drug-drug interactions. Expert Opin Drug Metab Toxicol. 10:1585–1605. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Rysz J, Franczyk B, Radek M, Ciałkowska-Rysz A and Gluba-Brzózka A: Diabetes and cardiovascular risk in renal transplant patients. Int J Mol Sci. 22:34222021. View Article : Google Scholar : PubMed/NCBI

23 

Drachenberg CB, Klassen DK, Weir MR, Wiland A, Fink JC, Bartlett ST, Cangro CB, Blahut S and Papadimitriou JC: Islet cell damage associated with tacrolimus and cyclosporine: Morphological features in pancreas allograft biopsies and clinical correlation. Transplantation. 68:396–402. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Soleimanpour SA, Crutchlow MF, Ferrari AM, Raum JC, Groff DN, Rankin MM, Liu C, De León DD, Naji A, Kushner JA and Stoffers DA: Calcineurin signaling regulates human islet {beta}-cell survival. J Biol Chem. 285:40050–40059. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Speckmann T, Sabatini PV, Nian C, Smith RG and Lynn FC: Npas4 transcription factor expression is regulated by calcium signaling pathways and prevents tacrolimus-induced cytotoxicity in pancreatic beta cells. J Biol Chem. 291:2682–2695. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Sottero B, Gargiulo S, Russo I, Barale C, Poli G and Cavalot F: Postprandial dysmetabolism and oxidative stress in type 2 diabetes: Pathogenetic mechanisms and therapeutic strategies. Med Res Rev. 35:968–1031. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Rehman K and Akash MSH: Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: How are they interlinked? J Cell Biochem. 118:3577–3585. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Aouacheri O, Saka S, Krim M, Messaadia A and Maidi I: The investigation of the oxidative stress-related parameters in type 2 diabetes mellitus. Can J Diabetes. 39:44–49. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Pérez Fernandez R, Martín Mateo MC, De Vega L, Bustamante Bustamante J, Herrero M and Bustamante Munguira E: Antioxidant enzyme determination and a study of lipid peroxidation in renal transplantation. Ren Fail. 24:353–359. 2002. View Article : Google Scholar

30 

Tsikas D: Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples, Analytical and biological challenges. Anal Biochem. 524:13–30. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Noberasco G, Odetti P, Boeri D, Maiello M and Adezati L: Malondialdehyde (MDA) level in diabetic subjects. Relationship with blood glucose and glycosylated hemoglobin. Biomed Pharmacother. 45:193–196. 1991. View Article : Google Scholar : PubMed/NCBI

32 

Yepes-Calderón M, Sotomayor CG, Gomes-Neto AW, Gans ROB, Berger SP, Rimbach G, Esatbeyoglu T, Rodrigo R, Geleijnse JM, Navis GJ and Bakker SJL: Plasma malondialdehyde and risk of new-onset diabetes after transplantation in renal transplant recipients: A prospective cohort study. J Clin Med. 8:4532019. View Article : Google Scholar

33 

Jin J, Jin L, Luo K, Lim SW, Chung BH and Yang CW: Effect of empagliflozin on tacrolimus-induced pancreas islet dysfunction and renal injury. Am J Transplant. 17:2601–2616. 2017. View Article : Google Scholar : PubMed/NCBI

34 

Ho E, Karimi Galougahi K, Liu CC, Bhindi R and Figtree GA: Biological markers of oxidative stress: Applications to cardiovascular research and practice. Redox Biol. 1:483–491. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Vivanco I and Sawyers CL: The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2:489–501. 2002. View Article : Google Scholar : PubMed/NCBI

36 

Engelman JA: Targeting PI3K signalling in cancer: Opportunities, challenges and limitations. Nat Rev Cancer. 9:550–562. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Whiteman EL, Cho H and Birnbaum MJ: Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab. 13:444–451. 2002. View Article : Google Scholar : PubMed/NCBI

38 

Asano T, Fujishiro M, Kushiyama A, Nakatsu Y, Yoneda M, Kamata H and Sakoda H: Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions. Biol Pharm Bull. 30:1610–1616. 2007. View Article : Google Scholar : PubMed/NCBI

39 

Matheny RW Jr and Adamo ML: PI3K p110 alpha and p110 beta have differential effects on Akt activation and protection against oxidative stress-induced apoptosis in myoblasts. Cell Death Differ. 17:677–688. 2010. View Article : Google Scholar : PubMed/NCBI

40 

Chen XW, Leto D, Xiong T, Yu G, Cheng A, Decker S and Saltiel AR: A Ral GAP complex links PI 3-kinase/Akt signaling to RalA activation in insulin action. Mol Biol Cell. 22:141–152. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Sudarsanam S and Johnson DE: Functional consequences of mTOR inhibition. Curr Opin Drug Discov Devel. 13:31–40. 2010.PubMed/NCBI

42 

Rodriguez-Rodriguez AE, Donate-Correa J, Rovira J, Cuesto G, Luis-Ravelo D, Fernandes MX, Acevedo-Arozena A, Diekmann F, Acebes A, Torres A and Porrini E: Inhibition of the mTOR pathway: A new mechanism of β cell toxicity induced by tacrolimus. Am J Transplant. 19:3240–3249. 2019. View Article : Google Scholar : PubMed/NCBI

43 

Slobodin B, Han R, Calderone V, Vrielink JAFO, Loayza-Puch F, Elkon R and Agami R: Transcription impacts the efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation. Cell. 169:326–337.e12. 2017. View Article : Google Scholar : PubMed/NCBI

44 

Juan Khong M and Ping Chong Ch: Prevention and management of new-onset diabetes mellitus in kidney transplantation. Neth J Med. 72:127–134. 2014.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tong L, Li W, Zhang Y, Zhou F, Zhao Y, Zhao L, Liu J, Song Z, Yu M, Zhou C, Zhou C, et al: Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway. Mol Med Rep 24: 658, 2021.
APA
Tong, L., Li, W., Zhang, Y., Zhou, F., Zhao, Y., Zhao, L. ... Yu, A. (2021). Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway. Molecular Medicine Reports, 24, 658. https://doi.org/10.3892/mmr.2021.12297
MLA
Tong, L., Li, W., Zhang, Y., Zhou, F., Zhao, Y., Zhao, L., Liu, J., Song, Z., Yu, M., Zhou, C., Yu, A."Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway". Molecular Medicine Reports 24.3 (2021): 658.
Chicago
Tong, L., Li, W., Zhang, Y., Zhou, F., Zhao, Y., Zhao, L., Liu, J., Song, Z., Yu, M., Zhou, C., Yu, A."Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway". Molecular Medicine Reports 24, no. 3 (2021): 658. https://doi.org/10.3892/mmr.2021.12297
Copy and paste a formatted citation
x
Spandidos Publications style
Tong L, Li W, Zhang Y, Zhou F, Zhao Y, Zhao L, Liu J, Song Z, Yu M, Zhou C, Zhou C, et al: Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway. Mol Med Rep 24: 658, 2021.
APA
Tong, L., Li, W., Zhang, Y., Zhou, F., Zhao, Y., Zhao, L. ... Yu, A. (2021). Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway. Molecular Medicine Reports, 24, 658. https://doi.org/10.3892/mmr.2021.12297
MLA
Tong, L., Li, W., Zhang, Y., Zhou, F., Zhao, Y., Zhao, L., Liu, J., Song, Z., Yu, M., Zhou, C., Yu, A."Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway". Molecular Medicine Reports 24.3 (2021): 658.
Chicago
Tong, L., Li, W., Zhang, Y., Zhou, F., Zhao, Y., Zhao, L., Liu, J., Song, Z., Yu, M., Zhou, C., Yu, A."Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway". Molecular Medicine Reports 24, no. 3 (2021): 658. https://doi.org/10.3892/mmr.2021.12297
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team