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.

Background: Identification of appropriate biomarker involved in the pathophysiology of diabetes-associated cognitive decline in animal model is necessary. Glucose transporter 4 (GLUT4) is the component of insulin-dependent neuronal signaling pathway needed for maintaining cognitive function. It is highly expressed in hippocampal neurons. Objective: To investigate the effect of GLUT4 expression in hippocampal neurons on the spatial memory of diabetes-induced Rattus novergicus. Methods: This experimental study used 24 male Rattus novergicus divided into control groups terminated on day-0 (C0), 14 (C1) and 28 (C2) and diabetic groups terminated on day-0 (D0), 14 (D1) and 28 (D2). Diabetes was induced using streptozotocin injections intraperitoneally. Spatial memory (travel time) of rats was assessed on day-14 and 28. Brain tissue sampling was performed for assessment of GLUT4 expression using immunohistochemical methods. Significant differences in means of GLUT4 expression and travel time between groups on day-0, 14 and 28 as well as correlation between means of GLUT4 expression and travel time in D1 and D2 were analyzed statistically. Results: The mean of GLUT4 expression in diabetic group was significantly higher compared to control on day-14, but not on day-0 and 28. The immunohistochemical examination confirmed this results. There were no significant differences in mean of travel time between control and diabetic groups on day-14 and 28. There were no significant correlation between means of GLUT4 expression and travel time in diabetic groups on day-14 and 28. Conclusion: The GLUT4 expression of hippocampal neurons did not significantly affect spatial memory of diabetes-induced Rattus novergicus.