DOI: https://doi.org/10.24959/ubphj.20.279

Biochemical role of pancreatic NMDA receptors in the pathogenesis of carbohydrate metabolism disorders

Т. Briukhanova, L. Galuzinska

Abstract


According to World Health Organization expert estimates, type 2 diabetes mellitus (DM2) remains the most common disease, which characterized by persistent disorders of almost all metabolic links.

Aim. To conduct an analytical review of available literature on the biochemical role of pancreatic NMDA receptors in the pathogenesis of carbohydrate metabolism disorders.

Materials and methods. Open-source analysis of the academic and scientific literature.

Results and discussion. According to the examined data, modulation of the activity of extraneuronal receptors, such as pancreatic NMDA receptors, may affect the regulation of carbohydrate metabolism, in particular glucose-stimulated insulin secretion and blood glucose homeostasis. Therefore, it is considered to be of high relevance to study those drugs that block pancreatic receptors to use them as the basis in the creation of new antidiabetic drugs.

Conclusions. NMDAR antagonists can be considered as new potential antidiabetic drugs that not only normalize blood glucose levels, but also have a protective effect onto islet cells. The use of NMDAR antagonists as adjunctive therapy in diabetes mellitus pharmacological correction regimens may be useful in inhibiting disease progression.

Keywords


type 2 diabetes; insulin resistance; pancreatic NMDA receptors; carbohydrate metabolism

References


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GOST Style Citations


1.   Characterizationof pancreatic NMDA receptors as possible drug targets for diabetes treatment / J.Marquard et al. Nat Med. 2015. № 21 (4). P. 363–72. DOI: 10.1038/nm.3822 (Date of access: 20.08.2020).

 

2.   The NMDA receptors / ed by K. Hashimoto. Cham : Springer International Publishing, 2017.

 

3.   GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes / N. Soltani et al. Proc Natl Acad Sci U S A. 2011. № 108 (28). Р. 11692–7. DOI: 10.1073/pnas.1102715108 (Date of access: 20.08.2020).

 

4.   Rodriguez-Diaz R. Real-time detection of acetylcholine release from the human endocrine pancreas. Nat Protoc. 2012. № 7 (6). Р. 1015–23. DOI: 10.1038/nprot.2012.040 (Date of access: 20.08.2020).

 

5.   EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets / I. Konstantinova et al. Cell. 2007. № 129 (2). Р. 359–70. DOI: 10.1016/j.cell.2007.02.044 (Date of access: 20.08.2020).

 

6.   Platt S. R. The role of glutamate in central nervous system health and disease : a review. VetJ. 2007. № 173 (2). Р. 278–86. DOI: 10.1016/j.tvjl.2005.11.007 (Date of access: 20.08.2020).

 

7.   The Glial Glutamate Transporter 1 (GLT1) is expressed by Pancreatic beta-cells and prevents Glutamate-induced beta-cell death / Di Cairano E. S. et al. J Biol Chem. 2011. № 286 (16). Р. 14007–18. DOI: 10.1074/jbc.M110.183517 (Date of access: 20.08.2020).

 

8.   Reduction of plasma membrane glutamate transport potentiates insulin but not glucagon secretionin pancreatic islet cells / N. Feldmann et al. Mol Cell Endocrinol. 2011. № 338 (1–2). Р. 46–57. DOI: 10.1016/j.mce.2011.02.019 (Date of access: 20.08.2020).

 

9.   Insulin secretionis controlled by mGlu5 metabotropic glutamate receptors / M. Storto et al. Mol Pharmacol. 2006. № 69 (4). Р. 1234–41. DOI: 10.1124/mol.105.018390 (Date of access: 20.08.2020).

 

10. Otter S, Lammert E. Exciting times for pancreatic islets: Glutamate signaling in endocrine cells. Trends Endocrinol Metabolism. 2016. № 27 (3). Р. 177–88. DOI: 10.1016/j.tem.2015.12.004 (Date of access: 20.08.2020).

 

11. Glutamate acts as akey signal linking glucose metabolism to Incretin - cAMP action to amplify insulin secretion / G. Gheni et al. Cell Rep. 2014. № 9 (2). Р. 661–73. DOI: 10.1016/j.celrep.2014.09.030 (Date of access: 20.08.2020).

 

12. Glutamate is apositive autocrine signal for glucagon release / O. Cabrera et al. Cell Metab. 2008. № 7 (6). Р. 545–54. DOI: 10.1016/j.cmet.2008.03.004 (Date of access: 20.08.2020).

 

13. Conditional glucagon receptor overexpression hasmulti-faceted consequences for beta-cell function / B. Omar et al. Metabolism. 2014. № 63 (12). Р. 1568–76. doi: 10.1016/j.metabol.2014.09.004 (Date of access: 20.08.2020).

 

14. AMPA receptors regulateexocytosis and insulin release in pancreatic beta cells / Z. Y. Wu et al. Traffic. 2012. № 13 (8). Р. 1124–39. DOI: 10.1111/j.1600-0854.2012.01373.x (Date of access: 20.08.2020).

 

15. Hawkins R. A. The blood-brain barrier and glutamate. Am J Clin Nutr. 2009. № 90 (3). Р. 867–74. DOI: 10.3945/ajcn.2009.27462BB (Date of access: 20.08.2020).

 

16. Kalia L. V., Kalia S. K., Salter M. W. NMDA receptors in clinical neurology: excitatory times head. Lancet Neurol. 2008. № 7 (8). Р. 742–55. DOI: 10.1016/S1474-4422(08)70165-0 (Date of access: 20.08.2020).

 

17. Gupta K., Hardingham G. E., Chandran S. NMDA receptor-dependent glutamate excitotoxicityin human embryonic stem cell-derived neurons. Neurosci Lett. 2013. № 543. Р. 95–100. DOI: 10.1016/j.neulet.2013.03.010 (Date of access: 20.08.2020).

 

18. Lutz T. A., Meyer U. Amylin at the interface between metabolic and neurodegenerative disorders. Front Neurosci. 2015. № 9. Р. 216. DOI: 10.3389/fnins.2015.00216 (Date of access: 20.08.2020).

 

19. The role for endoplasmic reticulum stress in diabetes mellitus / D. L. Eizirik et al. Endocr Rev. 2008. № 29 (1). Р. 42–61. DOI: 10.1210/er.2007-0015 (Date of access: 20.08.2020)

 

20. IL-1beta and TNF-alpha induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase / Y. Huang et al. J Neurochem. 2013. № 125 (6). Р. 897–908. DOI: 10.1111/jnc.12263 (Date of access: 20.08.2020)

 

21. Paoletti P., Bellone C., Zhou Q. NMDA receptor subunit diversity : impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci. 2013. № 14 (6). Р. 383–400. DOI: 10.1038/nrn3504 (Date of access: 20.08.2020).

 

22. Amantadinereduces glucagon and enhances insulin secretion throughout the oral glucose tolerance test: central plus peripheral nervous system mechanisms / F. Lechin et al. Diabetes Metab Syndr Obes. 2009. № 2. Р. 203–13. DOI: 10.2147/dmsott.s7606 (Date of access: 20.08.2020)

 

23. Shen K. Z., Johnson S. W. Ca2+ influx through NMDA-gated channels activates ATP-sensitiveK+ currents through a nitric oxide-cGMP pathway in subthalamic neurons. J Neurosci. 2010. № 30 (5). Р. 1882–93. DOI: 10.1523/JNEUROSCI.3200-09.2010 (Date of access: 20.08.2020).

 

24. AMP kinase regulates K-ATP currentsevoked by NMDA receptor stimulation in rat subthalamic nucleus neurons / K. Z. Shen et al. Neuroscience. 2014. № 274. Р. 138–52. DOI: 10.1016/j.neuroscience.2014.05.031 (Date of access: 20.08.2020).

 

25. Donath M. Y. Targeting inflammation in the treatment of type 2 diabetes : time to start. Nat RevDrug Discov. 2014. № 13 (6). Р. 465–76. DOI: 10.1038/nrd4275 (Date of access: 20.08.2020).

 

26. Wollheim C. B. Maechler P. Beta cell glutamate receptor antagonists: novel oral antidiabetic drugs. Nat Med. 2015. № 21 (4). Р. 310–1. DOI: 10.1038/nm.3835 (Date of access: 20.08.2020).

 

27. Effects of dextromethorphanas add-on to sitagliptin on blood glucose and serum insulin concentrations inindividuals with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blinded,multiple crossover, single-dose clinical trial / J. Marquard et al. Diabetes Obes Metab. 2016. № 18 (1). Р. 100–3. DOI: 10.1111/dom.12576 (Date of access: 20.08.2020).

 

28. Garnock-Jones K. P. Dextromethorphan/quinidine : in pseudobulbar affect. CNS Drugs. 2011. № 25 (5). Р. 435–45. DOI: 10.2165/11207260-000000000-00000 (Date of access: 20.08.2020).

 

29. Dicpinigaitis P. V. Clinical perspective – cough : an unmet need. Curr Opin Pharmacol. 2015. № 22. Р. 24–8. DOI: 10.1016/j.coph.2015.03.001 (Date of access: 20.08.2020).

 

30. Werling L. L., Lauterbach E. C., Calef U. Dextromethorphan as a potential neuroprotective agent with unique mechanisms of action. Neurologist. 2007. № 13 (5). Р. 272–93. DOI: 10.1097/NRL.0b013e3180f60bd8 (Date of access: 20.08.2020).

 

31. Neuropsychotoxic and neuroprotectivepotentials of dextromethorphan and its analogs / E. J. Shin et al. J Pharmacol Sci. 2011. № 116 (2). Р. 137–48. DOI: 10.1254/jphs.11R02CR (Date of access: 20.08.2020).

 

32. Dextromethorphan reducesoxidative stress and inhibits atherosclerosis and neointima formation in mice / S. L. Liu et al. Cardiovasc Res. 2009. № 82 (1). Р. 161–9. DOI: 10.1093/cvr/cvp043 (Date of access: 20.08.2020).

 

33. Low-dose dextromethorphan, a NADPH oxidase inhibitor,reduces blood pressure and enhances vascular protection in experimental hypertension / T. C. Wu et al. PLoS One. 2012. № 7 (9). Р. 460–67. DOI: 10.1371/journal.pone.0046067 (Date of access: 20.08.2020).





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