Gene expression of Gck in alloxan-induced diabetic male rats: potential therapeutic role of beta-aminobutyric acid
Abstract
Diabetes mellitus is a complex metabolic disorder characterized by hyperglycemia. This study aimed to evaluate the protective effect of be ta-aminobutyric acid (BABA) on a lloxa n-induced diabetes in male rats. Furthermore, this study examined the crucial role of the G ck gene in diabetes development, elucidating its characteristics and exp ression levels in liver tissue by studying its effect on glucose , ALT, AST, MDA, GlP, GlP-1, and GCK pathways. For modeling diabetes mellitus, t hirty adult male rats were randomly assigned to six groups of five individuals each . The rats were 6–8 weeks old and weighed 140 – 160 g. Positive control was treated with 2 m L normal saline, while the n egative control was treated only with 50 mg/kg alloxan, and the other four groups were treated with 50 mg/kg of alloxan , then 50, 100, 150, 200 mg/kg of BABA respectively. Enzyme-linked immunosorbent assay (ELISA) was utilized to evaluate the serum levels of glucose, ALT, AST, MDA, GlP, GlP-1, and hepatic glycogen GCK, and hepatic Gck mRNA levels had been measured via the reverse transcription-quantitative polymerase chain reaction (qRT-PCR) technique in thirty adult male albino rats. Hepatic damage was stimulated in six groups for the research using a lloxan. The addition of BABA at four different concentrations lasted for one month. Blood and tissue samples were collected at the end of the experimental period, following overnight fasting. All assays were performed in technical triplicates to ensure data reliability and reproducibility. Control − showed significantly higher levels of glucose, liver enzymes ALT and AST, and the oxidative stress marker (MDA), with a decrease in metabolic activity markers (GlP, GlP-1, GCK) compared with Control+. Treatment with BABA at increasing doses (50, 100, 150, 200 mg/kg) led to a gradual improvement in all studied markers. Glucose, ALT, AST, and MDA levels significantly decreased, while GlP, GlP-1, and GCK significantly increased. The best results were achieved at the 200 mg/kg dose (Group D), where values approached normal levels. This study indicates the effectiveness of BABA in redu c ing liver dam age and oxidative stress and im proving metabolic balance in the alloxan-induced diabetes model.References
Alaebo, P. O., Onyeabo, C., Oriaku, C. E., Njoku, G. C., Iloanusi, D. U., & Ekwunoh, P. O. (2022). Hepato-protective effect and lipid profile of honey on alloxan-induced diabetic rats. Asian Journal of Research in Biochemistry, 10(1), 16–24.
Al-Dulaimy, E. A. M., & Jasim, M. A. (2022). Effect of non-protein amino acid (BABA) on gastrointestinal tissues of male rats and some negative enterobacteria. Journal of Pharmaceutical Negative Results, 13(S2), 31.
Ali, A. A., & Jasim, M. A. (2025). Effects of beta aminobutyric acid (BABA) on the gene expression profiles of rats with CCl4-induced hepatic injury. International Journal of Environmental Sciences, 11(2S), 372–383.
Amrolahi, Z., Avandi, S. M., & Khaledi, N. (2022). The effect of six weeks’ progressive resistance training on hippocampus BDNF gene expression and serum changes of TNF-α in diabetic wistar rats. Journal of Sport and Exercise Physiology, 15(1), 1–10.
Arif, A. I., Rmaidh, A. Y., Qaddoori, H. T., & Mohammad, S. Q. (2025). Importance of testosterone and cortisol in prediabetic and diabetic male patients in Diyala Governorate (Iraq). Regulatory Mechanisms in Biosystems, 16(2), e25070.
Chee, Y. J., & Dalan, R. (2024). Novel therapeutics for type 2 diabetes mellitus – a look at the past decade and a glimpse into the future. Biomedicines, 12(7), 1386.
Elderbi, M., Omar, A., Omar, H., Elburi, A., & Ibrahim, M. (2025). Consequences of alloxan-induced diabetes on certain hematological and hepatic parameters in albino mice. Khalij-Libya Journal of Dental and Medical Research, 9(1), 38–43.
Eldib, A. M., Khedr, Y. I., El-Saad, A. M. A., Ghoneum, M., El-Gerbed, M. S. A., Babikir, I. H., & Altom, S. M. (2025). Modulatory effects of chitosan nanoparticles against alloxan-induced diabetes in rats. Advances in Animal and Veterinary Sciences, 13(6), 1355–1368.
Fikry, H., Saleh, L. A., Sadek, D. R., & Alkhalek, H. A. A. (2024). The possible protective effect of luteolin on cardiovascular and hepatic changes in metabolic syndrome rat model. Cell and Tissue Research, 399(1), 27–60.
Ghasemi, A., & Jeddi, S. (2023). Streptozotocin as a tool for induction of rat models of diabetes: A practical guide. Excli Journal, 22, 274–294.
Ghorbani, A., Rashidi, R., & Shafiee-Nick, R. (2019). Flavonoids for presserving pancreatic beta cell survival and function: A mechanistic review. Biomedicine and Pharmacotherapy, 111, 947–957.
Haddad, D., Dsouza, V. S., Al-Mulla, F., & Al Madhoun, A. (2024). New-generation glucokinase activators: Potential game-changers in type 2 diabetes treatment. International Journal of Molecular Sciences, 25(1), 571.
Hamad, A. I., & Jasim, M. A. (2024). Effect of β-aminobutyric acid (BABA) on Staphylococcus aureus and selected interleukins. Journal of University of Anbar for Pure Science, 18(1), 140–146.
Ighodaro, O. M., Adeosun, A. M., & Akinloye, O. A. (2017). Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina, 53(6), 365–374.
Khorrami, M. B., Sadeghnia, H. R., Pasdar, A., Ghayour-Mobarhan, M., Riahi-Zanjani, B., Hashemzadeh, A., Zare, M., & Darroudi, M. (2019). Antioxidant and toxicity studies of biosynthesized cerium oxide nanoparticles in rats. International Journal of Nanomedicine, 14, 2915–2926.
Lee, D.-Y., & Kim, E.-H. (2019). Therapeutic effects of amino acids in liver diseases: Current studies and future perspectives. Journal of Cancer Prevention, 24(2), 72–78.
Mahmud, J. A., Hasanuzzaman, M., Khan, M. I. R., Nahar, K., & Fujita, M. (2020). β-Aminobutyric acid pretreatment confers salt stress tolerance in Brassica napus L. by modulating reactive oxygen species metabolism and methylglyoxal detoxification. Plants, 9(2), 241.
Malik, A. W., Abood, A. A., & Mohammad, S. Q. (2023). Association between the proinflammatory cytokine IL-17F and Helicobacter pylori infection in a sample of Iraqi patients. International Journal of Biomedicine, 13(2), 338–341.
Martemucci, G., Costagliola, C., Mariano, M., D’andrea, L., Napolitano, P., & D’Alessandro, A. G. (2022). Free radical properties, source and targets, antioxidant consumption and health. Oxygen, 2(2), 48–78.
Matschinsky, F. M., & Wilson, D. F. (2019). The central role of glucokinase in glucose homeostasis: A perspective 50 years after demonstrating the presence of the enzyme in islets of langerhans. Frontiers in Physiology, 10, 148.
Miao, X.-Y., Gu, Z.-Y., Liu, P., Hu, Y., Li, L., Gong, Y.-P., Shu, H., Liu, Y., & Li, C.-L. (2013). The human glucagon-like peptide-1 analogue liraglutide regulates pancreatic beta-cell proliferation and apoptosis via an AMPK / mTOR / P70S6K signaling pathway. Peptides, 39, 71–79.
Mistry, J., Biswas, M., Sarkar, S., & Ghosh, S. (2023). Antidiabetic activity of mango peel extract and mangiferin in alloxan-induced diabetic rats. Future Journal of Pharmaceutical Sciences, 9(1), 22.
Mohammed, S. M., Abd-Almonuim, A. E., Majeed, A., & Khlaf, H. (2021). The anti-diabetic and anti-hyperlipidemia effect of Citrus maxima fruit peel extract in streptozotocin-induced diabetic rats. Research Journal of Pharmacy and Technology, 5355–5358.
Müller, T. D., Finan, B., Bloom, S. R., D’Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., Holst, J. J., Langhans, W., Meier, J. J., Nauck, M. A., Perez-Tilve, D., Pocai, A., Reimann, F., Sandoval, D. A., Schwartz, T. W., … Tschöp, M. H. (2019). Glucagon-like peptide 1 (GLP-1). Molecular Metabolism, 30, 72–130.
Park, K., Oh, M., Joo, Y., & Han, J.-K. (2023). Effects of gamma aminobutyric acid on performance, blood cell of broiler subjected to multi-stress environments. Animal Bioscience, 36(2), 248–255.
Setiawati, H., Djabir, Y. Y., Hardi, H., Lallo, S., & Cangara, M. H. (2022). Potential use of breadfruit (Artocarpus altilis) leaf extract to recover hepatic and renal damage in alloxan-induced diabetic rats. Fabad Eczacılık Bilimleri Dergisi, 47(2), 151–160.
Thamer, I. A. R. H., & Jasim, M. A. (2021). Anti-diabetic effect of β-aminobutyric acid in streptozotocin-induced rats. Systematic Reviews in Pharmacy, 12(2), 139–144.
Tiwari, M., & Singh, P. (2024). Bolstering wheat immunity: BABA-mediated defense priming against Bipolaris sorokiniana. Physiological and Molecular Plant Pathology, 133, 102372.
Yao, Y., Ji, K., Wang, Y., Gu, Z., & Wang, J. (2022). Materials and carriers development for glucose-responsive insulin. Accounts of Materials Research, 3(9), 960–970.
Zhang, W., Wu, L., Qu, R., Liu, T., Wang, J., Tong, Y., Bei, W., Guo, J., & Hu, X. (2024). Hesperidin activates the GLP-1R/cAMP-CREB/IRS2/PDX1 pathway to promote transdifferentiation of islet α cells into β cells across the spectrum. Heliyon, 10(16), e35424.
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