Modulation of insulin secretion and lipid profiles through glutamate dehydrogenase activators in diabetic rabbits

Document Type : Research Paper

Authors

1 Institute of Genetics and Physiology CS MSHE RK, Almaty, Kazakhstan & Al-Farabi Kazakh National University, Almaty, Kazakhstan

2 Institute of Natural Sciences and Geography, Abai Kazakh National pedagogical university, Almaty, Kazakhstan & 13, Dostyk Av., 050010 Almaty, the Republic of Kazakhstan

3 Faculty of Natural Sciences, Zhetysu University named after I. Zhansugurov Republic of Kazakhstan

4 Department of Anatomy with Physiology Courses, Kazakh-Russian Medical University, Almaty, Kazakhstan 13, Torekulova St., 050004 Almaty, the Republic of Kazakhstan

5 Abai Kazakh National Pedagogical University named after Abai. Department of Biology, 050010, Republic of Kazakhstan, Kazakhstan

6 Al-Farabi Kazakh National University, Almaty, Kazakhstan

7 Institute of Natural Sciences and Geography of the Kazakh National Pedagogical University named after Abai, Almaty, Kazakhstan; Republic of Kazakhstan, Kazakhstan

10.22124/cjes.2023.7415

Abstract

Diabetes mellitus is a prevalent metabolic disorder characterized by impaired insulin secretion and aberrant lipid metabolism. Targeting glutamate dehydrogenase (GDH) activators has emerged as a potential therapeutic strategy in managing diabetes. This study aims to investigate the effects of GDH activators on insulin secretion and lipid profiles in diabetic rabbits. Utilizing Streptozotocin (STZ) to induce diabetes in male New Zealand White rabbits, the impacts of three different GDH activators—Metformin, Epigallocatechin Gallate (EGCG), and Leucine—were examined. The subjects were categorized into five groups, including a diabetic control, a sham group, and three treatment groups administered with Metformin (5 mg kg-1), EGCG (15 mg kg-1), and Leucine (15 mg kg-1), respectively. The study reveals significant modulations in insulin and lipid profiles due to these treatments. In the Metformin-treated group, blood glucose levels significantly decreased during the second (p < 0.001) and third (p<0.01) weeks. The EGCG group exhibited a significant increase in insulin levels (p < 0.001), but no notable change in blood glucose. Conversely, the Leucine group showed an increase in triglyceride levels (p < 0.05) and a significant decrease in blood glucose levels (p < 0.01). Additionally, Metformin led to a substantial reduction in triglycerides (p < 0.001), while EGCG and Leucine were effective in lowering LDL levels (p < 0.01). Cholesterol and HDL levels remained relatively unchanged across all groups. These findings suggest that GDH activators, i.e., Metformin, EGCG, and Leucine, significantly impact insulin secretion and lipid metabolism, offering novel insights into diabetes management. This study not only demonstrates the therapeutic potential of these agents, but also emphasizes the importance of GDH pathways in diabetes research, providing a foundation for future investigations into metabolic regulation and treatment.
 

Keywords


Akinlade, OM, Owoyele, BV & Soladoye, AO 2021, Streptozotocin-induced type 1 and 2 diabetes in rodents: A model for studying diabetic cardiac autonomic neuropathy. African Health Sciences, 21: 719-727.
Alexopoulos, A-S, Qamar, A, Hutchins, K, Crowley, MJ, Batch, BC & Guyton, JR 2019, Triglycerides: Emerging Targets in Diabetes Care? Review of Moderate Hypertriglyceridemia in Diabetes. Current Diabetes Reports, 19: 13.
Aziz Mahdi Al-badry, F 2022, Physiological disturbances and histological damages of reproductive system in male rats resulted by metformin. Caspian Journal of Environmental Sciences, 20: 739-746.
Bian, Y, Hou, W, Chen, X, Fang, J, Xu, N, & Ruan, BH 2022, Glutamate Dehydrogenase as a Promising Target for Hyperinsulinism Hyperammonemia Syndrome Therapy. Current Medicinal Chemistry, 29: 2652-2672.
Casanova, E, Salvadó, J, Crescenti, A, & Gibert-Ramos, A 2019, Epigallocatechin gallate modulates muscle homeostasis in type 2 diabetes and obesity by targeting energetic and redox pathways: a narrative review. International Journal of Molecular Sciences, 20: 532.
Chang, SN, Keretsu, S & Kang, SC 2022, Evaluation of decursin and its isomer decursinol angelate as potential inhibitors of human glutamate dehydrogenase activity through in silico and enzymatic assay screening. Computers in Biology and Medicine, 151: 106287.
Cloete, L 2021, Diabetes mellitus: An overview of the types, symptoms, complications and management. Nursing Standard (Royal College of Nursing (Great Britain): 1987, 37: 61-66.
Cochran, BJ, Ong, K-L, Manandhar, B & Rye, KA 2021, High density lipoproteins and diabetes. Cells, 10: 850.
Davidson, WS, & Shah, AS 2019, High-density lipoprotein subspecies in health and human disease: focus on type 2 diabetes. Methodist DeBakey cardiovascular journal, 15: 55.
Dubey, P, Thakur, V & Chattopadhyay, M 2020, Role of minerals and trace elements in diabetes and insulin resistance. Nutrients, 12: 1864.
Furman, BL 2021, Streptozotocin‐induced diabetic models in mice and rats. Current Protocols, 1(4):e78.
Humaidan Al-Moussawi, NH 2022, Hormonal and enzymatic analysis for pancreas of diabetic and obese mice in Iraq. Caspian Journal of Environmental Sciences, 20: 337-349.
Li, L, Pan, M, Pan, S, Li, W, Zhong, Y, Hu, J, & Nie, S 2020, Effects of insoluble and soluble fibers isolated from barley on blood glucose, serum lipids, liver function and caecal short-chain fatty acids in type 2 diabetic and normal rats. Food and Chemical Toxicology, 135: 110937.
Li, Y, Guo, S, Yang, F, Liu, L & Chen, Z 2021, Huayu Tongluo recipe attenuates renal oxidative stress and inflammation through the activation of AMPK/Nrf2 signaling pathway in streptozotocin-(STZ-) induced diabetic rats. Evidence-based Complementary and Alternative Medicine, https://www.hindawi. com/journals/ecam/2021/5873007/ Date of access: 13 Nov. 2023.
Losada-Barragán, M 2021, Physiological effects of nutrients on insulin release by pancreatic beta cells. Molecular and Cellular Biochemistry, 476: 3127-3139.
Mitchelson, F, Safley, SA, Gordon, K, Weber, CJ & Sambanis, A 2021, Peritoneal dissolved oxygen and function of encapsulated adult porcine islets transplanted in streptozotocin diabetic mice. Xenotransplantation, 28: e12673.
Mukhtar, Y, Galalain, A & Yunusa, Ujej 2020, A modern overview on diabetes mellitus: a chronic endocrine disorder. European Journal of Biology, 5(2):1–14.
Park, S, Kang, HJ, Jeon, JH, Kim, MJ & Lee, IK 2019, Recent advances in the pathogenesis of microvascular complications in diabetes. Archives of Pharmacal Research, 42: 252-262.
Perego, C, Da Dalt, L, Pirillo, A, Galli, A, Catapano, AL & Norata, GD 2019, Cholesterol metabolism, pancreatic β-cell function and diabetes. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1865: 2149-2156.
Petraki, Z, Droubogiannis, S, Mylonaki, K, Chlouverakis, G, Plaitakis, A & Spanaki, C 2019, Transgenic expression of the positive selected human GLUD2 gene improves in vivo glucose homeostasis by regulating basic insulin secretion. Metabolism, 100: 153958.
Poznyak, A, Grechko, AV, Poggio, P, Myasoedova, VA, Alfieri, V & Orekhov, AN 2020, The diabetes mellitus–atherosclerosis connection: The role of lipid and glucose metabolism and chronic inflammation. International journal of molecular sciences, 21: 1835.
Rizvi, AA, Stoian, AP, Janez, A & Rizzo, M 2021, Lipoproteins and cardiovascular disease: an update on the clinical significance of atherogenic small, dense LDL and new therapeutical options. Biomedicines, 9:1579.
Rohm, TV, Meier, DT, Olefsky, JM & Donath, MY 2022, Inflammation in obesity, diabetes, and related disorders. Immunity, 55: 31-55.
Sainero-Alcolado, L, Liaño-Pons, J, Ruiz-Pérez, MV & Arsenian-Henriksson, M 2022, Targeting mitochondrial metabolism for precision medicine in cancer. Cell Death & Differentiation, 29: 1304-1317.
Wang, K, Song, F, Xu, K, Liu, Z, Han, S, Li, F & Sun, Y 2019, Irisin attenuates neuroinflammation and prevents the memory and cognitive deterioration in streptozotocin-induced diabetic mice. Mediators of inflammation, 2019 https://www.hindawi.com/journals/mi/2019/1567179/ Date of access: 13 Nov. 2023.
Wondmkun, YT 2020, Obesity, insulin resistance, and type 2 diabetes: Associations and therapeutic implications. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Volume 13: 3611-3616.
Zeng, Q & Sang, Y-M 2023, Glutamate dehydrogenase hyperinsulinism: mechanisms, diagnosis, and treatment. Orphanet Journal of Rare Diseases, 18: 21.