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Pengaruh kadar gula darah puasa terhadap ekspresi Glucose transporter type-4 (GLUT4) neuron hipokampus pada tikus model diabetes

Abstract

Background: Diabetes mellitus causes many complications, both microvascular and macrovascular, especially cognitive function. Related studies are being carried out to determine the relationship between diabetes and cognitive decline as assessed through GLUT4 expression in the hippocampus. The aimed of this study was to determine the effect of fasting blood sugar on hippocampal neuronal GLUT4 expression in STZ and NA-induced diabetic rats.

Methods: This study was an experimental design, using 24 males Rattus novergicus which were divided into a control group terminated on day 14 (A0) and 28 (B0) and a diabetes group terminated on day 14 (A1) and 28 (B2). Diabetes was induced using intraperitoneal injection of streptozotocin (STZ) and Nicotinamide (NA). Spatial memory (travel time) of rats was assessed on days 14 and 28. Sampling used secondary data, fasting blood glucose (FBG) was measured using a glucometer and brain tissue was taken to assess GLUT4 expression using immunohistochemical methods. Differences in the mean FBG and GLUT4 expression between groups on days 14 and 28 and were tested statistically using SPSS version 22

Results: The mean FBG and GLUT4 expression in the diabetic group were significantly higher than those in the control group on day 14 and day 28. However, it was not significant compared between diabetes groups on day 14 and day 28. Immunohistochemical examination confirmed these results. There is a strong correlation between mean FBG levels and mean GLUT4 expression with travel time in the diabetes group on days 14 and 28 (r=0.88, p<0.05).

Conclusion: Fasting blood glucose levels significantly affected hippocampal neuronal GLUT4 expression in STZ and NA-induced diabetic rats.

 

Latar belakang: Diabetes mellitus banyak menimbulkan komplikasi serius baik mikrovaskuler dan makrovaskuler, khususnya pada fungsi kognitif. Studi terkait sedang terus dilaksanakan untuk mengetahui hubungan terkait antara kondisi diabetes dengan penurunan fungsi kognitif yang dinilai memalui ekspresi GLUT4 di hippocampus. Tujuan dari penelitian ini adalah untuk mengevaluasi pengaruh kadar gula darah puasa terhadap ekspresi GLUT4 neuron hipokampus pada tikus model diabetes.

Metode: Penelitian dengan desain eksperimental, menggunakan 24 ekor Rattus novergicus jantan yang dibagi menjadi kelompok kontrol yang diterminasi pada hari ke-14 (A0) dan 28 (B0) dan kelompok diabetes yang diterminasi pada hari ke-14 (A1) dan 28 (B2). Diabetes diinduksi menggunakan suntikan streptozotocin (STZ) dan Nikotinamid (NA) secara intraperitoneal. Memori spasial (waktu tempuh) tikus dinilai pada hari ke-14 dan 28. Pengambilan sampel menggunakan data sekunder, gula darah puasa (GDP) diukur menggunakan glucometer dan pengambilan jaringan otak dilakukan untuk penilaian ekspresi GLUT4 menggunakan metode imunohistokimia. Perbedaan rerata GDP dan ekspresi GLUT4 antar kelompok pada hari ke-14 dan 28 serta dilakukan uji secara statistik menggunakan SPSS versi 22.

Hasil: Rerata GDP dan ekspresi GLUT4 pada kelompok diabetes secara signifikan lebih tinggi dibandingkan dengan kontrol pada hari ke-14 maupun hari ke 28. Akan tetapi tidak signifikan dibandingkan antar kelompok diabetes pada hari ke-14 dengan hari ke-28. Pemeriksaan imunohistokimia mengkonfirmasi hasil ini. Terdapat korelasi yang kuat pada hubungan yang rerata kadar GDP dengan rerata ekspresi GLUT4 dengan waktu tempuh pada kelompok diabetes pada hari ke-14 dan 28 (r=0,88, p<0,05).

Simpulan: Kadar gula darah puasa berpengaruh secara signifikan terhadap ekspresi GLUT4 neuron hipokampus pada tikus model.

References

  1. Kharroubi AT, Darwish HM. Diabetes mellitus: The epidemic of the century. World J Diabetes 6 (6): 850–867.
  2. Wilcox G. Insulin and insulin resistance. Clinical biochemist reviews. 2005;26(2):19.
  3. Kahanovitz L, Sluss PM, Russell SJ. Type 1 diabetes–a clinical perspective. Point of care. 2017 Mar;16(1):37.
  4. WHO. Global report on diabetes. 2016; 978:92–4. Available at: http://www.who.int/about/licensing/copyright_form/index.html%0Ahttp://www.who.int/about/licensing/.
  5. RISKESDAS. Riset Kesehatan Dasar 2013. 2013. Jakarta: Badan Penelitian dan Pengembangan Kesehatan Kementrian Kesehatan RI.
  6. RISKESDAS. Riset Kesehatan Dasar. 2018. Jakarta: Badan Penelitian dan Pengembangan Kesehatan Kementrian Kesehatan RI.
  7. Brunetti L, Kalabalik J. Management of type-2 diabetes mellitus in adults: focus on individualizing non-insulin therapies. Pharmacy and therapeutics. 2012;37(12):687.
  8. Sadeghi A, Hami J, Razavi S, Esfandiary E, Hejazi Z. The effect of diabetes mellitus on apoptosis in hippocampus: cellular and molecular aspects. International journal of preventive medicine. 2016;7.
  9. Baynes HW. Classification, pathophysiology, diagnosis and management of diabetes mellitus. J diabetes metab. 2015 May 1;6(5):1-9.
  10. Zhang H, Ni J, Yu C, Wu Y, Li J, Liu J, Tu J, Ning X, He Q, Wang J. Sex-based differences in diabetes prevalence and risk factors: a population-based cross-sectional study among low-income adults in China. Frontiers in Endocrinology. 2019:658.
  11. Sudoyo, Aru W, et al. Buku Ajar Ilmu Penyakit Dalam. 2014; Jilid I Edisi VI. Jakarta: Interna Publishing 2014.
  12. American Diabetes Association. Updates to the Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018; 41(9):2045–2047. https://doi.org/10.2337/dc18-su09
  13. Liu Z, Zaid M, Hisamatsu T, Tanaka S, Fujiyoshi A, Miyagawa N, Ito T, Kadota A, Tooyama I, Miura K, Ueshima H. Elevated fasting blood glucose levels are associated with lower cognitive function, with a threshold in non-diabetic individuals: a population-based study. Journal of epidemiology. 2020;30(3):121-7.
  14. Long W, Cheeseman CI. Structure of, and functional insight into the GLUT family of membrane transporters. Cell Health Cytoskelet 7: 167–183.
  15. Shah K, DeSilva S, Abbruscato T. The role of glucose transporters in brain disease: diabetes and Alzheimer’s disease. International journal of molecular sciences. 2012;13(10):12629-55.
  16. Alquier, Thierry & Leloup, Corinne & Anne, Lorsignol & Pénicaud, Luc. Translocable Glucose Transporters in the Brain: Where Are We in 2006?. Diabetes. 2006; 55. 10.2337/db06-S021.
  17. Vannucci, S. J., Koehler-Stec, E. M., Li, K., Reynolds, T. H., Clark, R., & Simpson, I. A. GLUT4 glucose transporter expression in rodent brain: effect of diabetes. Brain research. 1998; 797(1):1–11. https://doi.org/10.1016/s0006-8993(98)00103-6
  18. Reno, C. M., Puente, E. C., Sheng, Z., Daphna-Iken, D., Bree, A. J., Routh, V. H., Kahn, B. B., & Fisher, S. J. Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation. Diabetes. 2017; 66(3): 587–597. https://doi.org/10.2337/db16-0917
  19. Harahap HS, Novrita Padauleng, Rizka Vidya Lestari, Nurhidayati Nurhidayati, Anak Agung Ayu Niti Wedayani, Putu Suwita Sari, Hifdzil Haq Muliyana, Ngakan Putu Proudy Laksmana, Aliza Raudatin Sahly. The Effect Of Glut4 Expression In Hippocampal Neurons To Spatial Memory Of Diabetes- Induced Rattus Novergicus. Malang Neurology Journal.2021; 114-119.
  20. Hird, T. R., Pirie, F. J., Esterhuizen, T. M., O'Leary, B., McCarthy, M. I., Young, E. H., Sandhu, M. S., & Motala, A. A. Burden of Diabetes and First Evidence for the Utility of HbA1c for Diagnosis and Detection of Diabetes in Urban Black South Africans: The Durban Diabetes Study. PloS one. 2016; 11(8): e0161966. https://doi.org/10.1371/journal.pone.0161966
  21. Kishore L, Kajal A, Kaur N. Role of Nicotinamide in Streptozotocin Induced Diabetes in Animal Models. J Endocrinol Thyroid Res; 2017. 2(1):555577. DOI: 10.19080/jetr.2017.02.555577
  22. Cheng Y, Kang H, Shen J, Hao H, Liu J, Guo Y, Mu Y, Han W. Beta-cell regeneration from vimentin+/MafB+ cells after STZ-induced extreme beta-cell ablation. Scientific reports. 2015;5(1):1-2.
  23. Zhang Y, Zhang Y, Bone RN, Cui W, Peng JB, et al. (2012) Regeneration of Pancreatic Non-β Endocrine Cells in Adult Mice following a Single Diabetes-Inducing Dose of Streptozotocin. PLOS ONE 7(5): e36675. https://doi.org/10.1371/journal.pone.0036675
  24. Harahap HS, Padauleng N, Nurhidayati N, Ekawanti A. Ekspresi GLUT4 pada Neuron Hipokampus Rattus novergicus Diabetik yang Diinjeksi Streptozotocin dan Nicotinamide. Jurnal Kedokteran Brawijaya. 2019;30(3):197-201.
  25. Pearson-Leary, J., & McNay, E. C. Novel Roles for the Insulin-Regulated Glucose Transporter-4 in Hippocampally Dependent Memory. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2016;36(47):11851–11864. https://doi.org/10.1523/JNEUROSCI.1700-16.2016
  26. Satyarsa ABS. Potential effects of alkaloid vindolicine substances in tapak dara leafs (Catharanthus roseus (L.) G. Don) in reducing blood glucose levels. Journal of Medicine and Health. 2019;2(4):1009-19. https://doi.org/10.28932/jmh.v2i4.1057
  27. Jasmin, Shahana & Ali, Mohammad & Ferdous, Mokerroma & Arslan, M. & Biswas, Subrata. Glucose transporter 4 gene expression in peripheral blood leukocytes in type 2 diabetes mellitus. Bangabandhu Sheikh Mujib Medical University Journal. 2019;12:19-24. 10.3329/bsmmuj.v12i1.40467
  28. Wedayani AA, Harahap HS. Korelasi Antara Ekspresi Glut4 Neuron Hipokampus Dan Travel Time Tikus Model Diabetes Tipe 2 Pada Pemeriksaan Morris Water Maze Dengan Waktu Pengamatan Yang Berbeda. Jurnal Kedokteran. 2020;9(1):13-22.

How to Cite

Proudy Laksmana, N. P., Lestari, R. V. ., Sahidu, M. G. ., Hunaifi, I. ., Harahap, H. S. ., Padauleng, N. ., & Nurhidayati. (2022). Pengaruh kadar gula darah puasa terhadap ekspresi Glucose transporter type-4 (GLUT4) neuron hipokampus pada tikus model diabetes. Intisari Sains Medis, 13(2), 321–327. https://doi.org/10.15562/ism.v13i2.1386

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Ngakan Putu Proudy Laksmana
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Rizka Vidya Lestari
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Muhammad Ghalvan Sahidu
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Ilsa Hunaifi
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Herpan Syafii Harahap
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Novrita Padauleng
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Nurhidayati
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