:: Volume 27, Issue 5 (Bimonthly 2023) ::
Feyz Med Sci J 2023, 27(5): 473-480 Back to browse issues page
Changes in protein expression of NMDA glutamate receptor and Pannexin-1 channel in gastric antrum tissue of rats with type 2 diabetes and treated with insulin
Hossein Rezazadeh Mehrizi , Nepton Soltani , Nasrin Mehranfard , Maedeh Ghasemi *
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran , ghasemi.m@med.mui.ac.ir
Abstract:   (2037 Views)
Background and Aim: Evidence shows that glutamate receptors play a role in the occurrence of gastrointestinal damage caused by diabetes. Therefore, in this study, the protein expression pattern of glutamate receptor N-methyl-D-aspartate (NMDA) and pannexin-1 (Panx-1) channel, which has an important functional relationship with glutamate receptors, in the stomach of type 2 diabetic rats were investigated. We also assessed the effect of long-term treatment with insulin on the possible changes of the mentioned proteins.
Methods: In this experimental study, 18 male Wistar rats weighing approximately 80-90 grams were randomly assigned into 3 groups (6 rats each): 1) control with standard diet, 2) type 2 diabetes: high-fat diet for 3 months + single dose of streptozotocin (35 mg/kg), and 3) type 2 diabetes + insulin treatment. The protein content of NMDA receptor as well as Panx-1 was detected using western blot method and compared among groups.
Results: In the stomach of type 2 diabetic rats, the expression of Panx-1 protein was significantly decreased (P<0.001), while the expression of NMDA receptor (P<0.001) showed a significant increase. Insulin treatment improved the expression level of Panx-1 protein in diabetic rats, in addition, insulin treatment decreased the expression level of NMDA receptor in diabetic rats (P<0.05).
Conclusion: The present findings indicate important changes in protein levels of NMDA receptor and Panx-1 channel and their possible role in the occurrence of sensory-motor and secretory damage related to diabetes. The correction of the above changes may play a role in improving the functional damage caused by type 2 diabetes.
Keywords: Type 2 diabetes, NMDA receptor, Pannexin-1 channel
Full-Text [PDF 503 kb]   (1478 Downloads)    
Type of Study: Research | Subject: medicine, paraclinic
Received: 2023/08/6 | Revised: 2023/12/13 | Accepted: 2023/10/17 | Published: 2023/12/10
References
1. Zavaleta MJC, Yovera JGG, Marreros DMM, Robles L del PR, Taype KRP, Gálvez KNS, et al. Diabetic gastroenteropathy: An underdiagnosed complication. World J Diabetes [Internet]. 2021 Jun 6 [cited 2023 Aug 6]; 12(6):794. Available at: /pmc/articles/PMC8192258/
2. Yang X, Lou J, Shan W, Ding J, Jin Z, Hu Y, et al. Pathophysiologic Role of Neurotransmitters in Digestive Diseases. Front Physiol [Internet]. 2021 Jun 14 [cited 2023 Aug 6];12:567650. Available at: /pmc/articles/PMC8236819/
3. Choi WM, Kim HH, Kim MH, Cinar R, Yi HS, Eun HS, et al. Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis. Cell Metab [Internet]. 2019 Nov 5 [cited 2023 Aug 6]; 30(5): 877-889.e7. Available at: https://pubmed.ncbi.nlm.nih.gov/ 31474565/
4. Shao L, Liu Y, Xiao J, Wang Q, Liu F, Ding J. Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats. Int J Mol Med [Internet]. 2019 Feb 1 [cited 2023 Aug 6];43(2):761–70. Available at: https://pubmed.ncbi.nlm.nih.gov/ 30569115/
5. Ishibashi-Shiraishi I, Shiraishi S, Fujita S, Ogawa S, Kaneko M, Suzuki M, et al. L-Arginine L-Glutamate Enhances Gastric Motor Function in Rats and Dogs and Improves Delayed Gastric Emptying in Dogs. J Pharmacol Exp Ther [Internet]. 2016 Nov 1 [cited 2023 Aug 6]; 359(2): 238–46. Available at: https://pubmed.ncbi.nlm.nih.gov/ 27535977/
6. Peterlik D, Stangl C, Bauer A, Bludau A, Keller J, Grabski D, et al. Blocking metabotropic glutamate receptor subtype 5 relieves maladaptive chronic stress consequences. Brain Behav Immun [Internet]. 2017 Jan 1 [cited 2023 Aug 6];59:79–92. Available at: https://pubmed.ncbi.nlm.nih.gov/27524668/
7. Tsai LH, Lee YJ, Wu JY. Role of N-methyl-D-aspartate receptors in gastric mucosal blood flow induced by histamine. J Neurosci Res [Internet]. 2004 Sep 1 [cited 2023 Aug 6]; 77(5):730–8. Available at: https://pubmed.ncbi.nlm.nih.gov/ 15352220/
8. Milusheva EA, Kuneva VI, Itzev DE, Kortezova NI, Sperlagh B, Mizhorkova ZN. Glutamate stimulation of acetylcholine release from myenteric plexus is mediated by endogenous nitric oxide. Brain Res Bull. 2005; 66(3):229–34.
9. Bravo D, Zepeda-Morales K, Maturana CJ, Retamal JS, Hernández A, Pelissier T, et al. NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats. Int J Mol Sci [Internet]. 2022; 23(12).Available at: /pmc/articles/PMC9223805/
10. Navis KE, Fan CY, Trang T, Thompson RJ, Derksen DJ. Pannexin 1 Channels as a Therapeutic Target: Structure, Inhibition, and Outlook. ACS Chem Neurosci [Internet]. 2020; 11(15): 2163–72. Available at: https://pubmed.ncbi.nlm.nih.gov/ 32639715/
11. Yeung AK, Patil CS, Jackson MF. Pannexin-1 in the CNS: Emerging concepts in health and disease. J Neurochem [Internet]. 2020; 154(5): 468–85. Available at: https://onlinelibrary.wiley.com/doi/full/ 10.1111/jnc.15004
12. Seo JH, Dalal MS, Contreras JE. Pannexin-1 Channels as Mediators of Neuroinflammation. Int J Mol Sci [Internet]. 2021; 22(10):5189. Available at: /pmc/articles/PMC8156193/
13. Crespo Yanguas S, Willebrords J, Johnstone SR, Maes M, Decrock E, De Bock M, et al. Pannexin1 as mediator of inflammation and cell death. Biochim Biophys Acta - Mol Cell Res. 2017; 1864(1): 51–61.
14. Gulbransen BD, Bashashati M, Hirota SA, Gui X, Roberts JA, MacDonald JA, et al. Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat Med [Internet]. 2012; 18(4): 600–4. Available at: https://pubmed.ncbi.nlm.nih.gov/ 22426419/
15. Diezmos EF, Markus I, Perera DS, Gan S, Zhang L, Sandow SL, et al. Blockade of Pannexin-1 Channels and Purinergic P2X7 Receptors Shows Protective Effects Against Cytokines-Induced Colitis of Human Colonic Mucosa. Front Pharmacol [Internet]. 2018; 9(AUG). Available at: https://pubmed.ncbi.nlm.nih.gov/ 30127744/
16. Zhang CM, Huang X, Lu HL, Meng XM, Song NN, Chen L, et al. Diabetes-induced damage of gastric nitric oxide neurons mediated by P2X7R in diabetic mice. Eur J Pharmacol. 2019; 851: 151–60.
17. Ying W, Zheng K, Wu Y, Wang O. Pannexin 1 Mediates Gastric Cancer Cell Epithelial-Mesenchymal Transition via Aquaporin 5. Biol Pharm Bull [Internet]. 2021; 44(8): 1111–9. Available at: https://pubmed.ncbi.nlm.nih.gov/ 34135208/
18. 18. Wu LY, Ye ZN, Zhou CH, Wang CX, Xie G Bin, Zhang XS, et al. Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats. Front Mol Neurosci [Internet]. 2017; 10.Available at: /pmc/articles/PMC5459922/
19. Hernandez CA, Eliseo E, Hernandez CA, Eliseo E. The Role of Pannexin-1 Channels in HIV and NeuroHIV Pathogenesis. Cells 2022, Vol 11, Page 2245 [Internet]. 2022; 11(14): 2245. Available at: https://www.mdpi.com/2073-4409/11/14/2245/htm
20. Kroon C, Breuer L, Jones L, An J, Akan A, Ali EAM, et al. Blind spots on western blots: Assessment of common problems in western blot figures and methods reporting with recommendations to improve them. PLoS Biol [Internet]. 2022; 20(9): Available at: https://pubmed.ncbi.nlm.nih.gov/36095010/
21. Rezazadeh H, Sharifi MR, Sharifi M, Soltani N. Gamma-aminobutyric acid attenuates insulin resistance in type 2 diabetic patients and reduces the risk of insulin resistance in their offspring. Biomed Pharmacother. 2021; 138: 111440.
22. Azpiroz F, Malagelada C. Diabetic neuropathy in the gut: pathogenesis and diagnosis. Diabetologia [Internet]. 2016; 59(3): 404–8. Available at: https://link.springer.com/article/10. 1007/s00125-015-3831-1
23. Golovynska I, Beregova T V., Falalyeyeva TM, Stepanova LI, Golovynskyi S, Qu J, et al. Peripheral N-methyl-D-aspartate receptor localization and role in gastric acid secretion regulation: immunofluorescence and pharmacological studies. Sci Rep [Internet]. 2018 Dec 1 [cited 2023 Aug 6];8(1). Available from: /pmc/articles/PMC5945873/
24. Tsai LH, Wu JY. Glutamate receptors in the stomach and their implications. Glutamate Recept Peripher Tissue Excit Transm Outs CNS [Internet]. 2005 [cited 2023 Aug 6];179–90. Available from: https://link.springer.com/chapter/10.1007/0-306-48644-X_10
25. Golovynska I, Beregova T V., Falalyeyeva TM, Stepanova LI, Golovynskyi S, Qu J, et al. Peripheral N-methyl-D-aspartate receptor localization and role in gastric acid secretion regulation: immunofluorescence and pharmacological studies. Sci Reports 2018 81 [Internet]. 2018 May 10 [cited 2023 May 16];8(1):1–11. Available at: https://www.nature.com/articles/s41598-018-25753-6
26. Wu CS, Lu YJ, Li HP, Hsueh C, Lu CY, Leu YW, et al. Glutamate receptor, ionotropic, kainate 2 silencing by DNA hypermethylation possesses tumor suppressor function in gastric cancer. Int J Cancer [Internet]. 2010 Jun 1 [cited 2023 Aug 6];126(11):2542–52. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.24958
27. Huang XT, Yang JX, Wang Z, Zhang CY, Luo ZQ, Liu W, et al. Activation of N-methyl-D-aspartate receptor regulates insulin sensitivity and lipid metabolism. 2021 [cited 2023 Aug 6];11(5):2247–62. Available at: http://www.thno.org// creativecommons.org/licenses/by/4.0/
28. Li S, Bjelobaba I, Stojilkovic SS. Interactions of Pannexin1 Channels with Purinergic and NMDA Receptor Channels. Biochim Biophys Acta [Internet]. 2018 Jan 1 [cited 2023 Aug 6]; 1860(1): 166. Available from: /pmc/articles/PMC5628093/
29. Thompson RJ. Pannexin channels and ischaemia. J Physiol [Internet]. 2015; 593(16):3463–70. Available at: https://pubmed.ncbi.nlm.nih.gov/ 25384783/
30. Kovalzon VM, Moiseenko LS, Ambaryan AV, Kurtenbach S, Shestopalov VI, Panchin YV. Sleep-wakefulness cycle and behavior in pannexin1 knockout mice. Behav Brain Res [Internet]. 2017; 318: 24–7. Available at: https://pubmed.ncbi.nlm.nih.gov/ 27769744/
31. Adamson SE, Meher AK, Chiu Y hsin, Sandilos JK, Oberholtzer NP, Walker NN, et al. Pannexin 1 is required for full activation of insulin-stimulated glucose uptake in adipocytes. Mol Metab [Internet]. 2015; 4(9): 610–8. Available at: https://pubmed.ncbi.nlm.nih.gov/ 26413467/



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Volume 27, Issue 5 (Bimonthly 2023) Back to browse issues page