Abstract
Background: Growing pieces of evidence demonstrate a close relationship between type 2 diabetes (T2D) and neurodegenerative disorders such as Alzheimer’s disease. The similarity of physiological and pathological processes occurring in pancreatic β-cells and neurons over the course of these pathologies allows raising the question of the practicability of studying neuroprotective substances for their potential antidiabetic activity.
Objective: This review analyzes studies of antidiabetic and cytoprotective action on pancreatic β- cells of the neuroprotective compounds that can attenuate the oxidative stress and enhance the expression of neurotrophins: low-molecular-weight NGF mimetic compound GK-2, selective anxiolytic afobazole, antidepressants lithium chloride, and lithium carbonate on the rat streptozotocin model of T2D.
Results: It was found that all the above-listed neuroprotective substances have a pronounced antidiabetic activity. The decrease in the β-cells number, the average area of the pancreatic islets, as well as the violation of their morphological structure caused by the streptozotocin was significantly weakened by the therapy with the investigated neuroprotective substances. The extent of these morphological changes clearly correlates with the antihyperglycemic effect of these compounds.
Conclusion: The presented data indicate that the neuroprotective substances attenuating the damaging effect of oxidative stress and neurotrophins deficit cannot only protect neurons but also exert their cytoprotective effect towards pancreatic β-cells. These data may provide a theoretical basis for the further study of neuroprotective drugs as potential therapeutic options for T2D prevention and treatment.
Keywords: Type 2 diabetes, cytoprotection, neuroprotection, β-cells, streptozotocin, neurotrophins.
Graphical Abstract
[http://dx.doi.org/10.1016/j.bbr.2017.11.015] [PMID: 29158110]
[http://dx.doi.org/10.2174/1871530319666190311141855] [PMID: 30854980]
[http://dx.doi.org/10.3390/ijms19113306] [PMID: 30355995]
[http://dx.doi.org/10.1186/s12929-017-0379-z] [PMID: 28927401]
[http://dx.doi.org/10.1002/med.21440] [PMID: 28422298]
[http://dx.doi.org/10.3389/fneur.2019.00649] [PMID: 31293498]
[http://dx.doi.org/10.1155/2019/1435276] [PMID: 31428627]
[http://dx.doi.org/10.1038/347151a0] [PMID: 1697648]
[http://dx.doi.org/10.1152/ajpregu.00776.2010] [PMID: 21346243]
[http://dx.doi.org/10.1016/j.tem.2015.12.004] [PMID: 26740469]
[http://dx.doi.org/10.2337/db09-0891] [PMID: 20009089]
[http://dx.doi.org/10.1172/JCI35846] [PMID: 20440072]
[http://dx.doi.org/10.1074/jbc.272.3.1929] [PMID: 8999882]
[http://dx.doi.org/10.1073/pnas.90.12.5781] [PMID: 8516328]
[http://dx.doi.org/10.5114/aoms.2015.56342] [PMID: 26788077]
[http://dx.doi.org/10.1016/j.cbpa.2010.01.019] [PMID: 20138234]
[http://dx.doi.org/10.1016/0016-6480(77)90055-7] [PMID: 924129]
[http://dx.doi.org/10.1002/dvdy.10460] [PMID: 14699589]
[http://dx.doi.org/10.1002/bies.201100015] [PMID: 21681773]
[PMID: 27350199]
[http://dx.doi.org/10.1186/s13063-019-3259-x] [PMID: 30944040]
[http://dx.doi.org/10.1016/j.diabres.2016.12.010] [PMID: 28056430]
[http://dx.doi.org/10.1111/cns.12404] [PMID: 26010513]
[http://dx.doi.org/10.1097/MJT.0000000000000926] [PMID: 30648990]
[http://dx.doi.org/10.1186/s13104-018-3715-9] [PMID: 30144824]
[http://dx.doi.org/10.1016/j.arr.2020.101095] [PMID: 32535272]
[http://dx.doi.org/10.1186/s12929-014-0074-2] [PMID: 25096780]
[http://dx.doi.org/10.1007/s10517-014-2562-5] [PMID: 25065315]
[PMID: 9483398]
[http://dx.doi.org/10.1023/A:1002828707337] [PMID: 11177296]
[http://dx.doi.org/10.1007/s10517-008-0297-x] [PMID: 19240853]
[http://dx.doi.org/10.1007/s11055-019-00806-z]
[http://dx.doi.org/10.1002/med.21721] [PMID: 32808322]
[http://dx.doi.org/10.3389/fnins.2019.00414] [PMID: 31156357]
[PMID: 22200861]
[http://dx.doi.org/10.3389/fnins.2014.00457] [PMID: 25642163]
[PMID: 26261558]
[http://dx.doi.org/10.1016/j.jdiacomp.2016.09.001] [PMID: 27662780]
[http://dx.doi.org/10.2337/diabetes.50.2007.S20] [PMID: 11272192]
[http://dx.doi.org/10.1007/s10495-011-0657-2] [PMID: 21938476]
[http://dx.doi.org/10.1080/08977190310001629566] [PMID: 14708938]
[http://dx.doi.org/10.1186/s12929-015-0198-z] [PMID: 26642930]
[PMID: 23901462]
[http://dx.doi.org/10.1134/S001249661302004X] [PMID: 23652431]
[http://dx.doi.org/10.1111/j.2040-1124.2010.00072.x] [PMID: 24843456]
[http://dx.doi.org/10.32607/20758251-2019-11-1-48-57] [PMID: 31024748]
[http://dx.doi.org/10.1007/s11094-019-02043-7]
[http://dx.doi.org/10.1007/s10517-014-2681-z] [PMID: 25403388]
[http://dx.doi.org/10.1007/s10517-018-4233-4] [PMID: 30225697]
[http://dx.doi.org/10.1007/s10517-020-04978-4] [PMID: 33098515]
[http://dx.doi.org/10.2174/1568008033340153] [PMID: 14683459]
[http://dx.doi.org/10.1007/s10517-018-4259-7] [PMID: 30353339]
[PMID: 21750398]
[http://dx.doi.org/10.1074/jbc.M117.808105] [PMID: 28972173]
[http://dx.doi.org/10.3390/ijms22010421] [PMID: 33401592]
[http://dx.doi.org/10.1152/ajpendo.00447.2016] [PMID: 28512156]
[http://dx.doi.org/10.1016/j.taap.2006.01.003] [PMID: 16490224]
[http://dx.doi.org/10.1016/j.biopha.2018.09.058] [PMID: 30245465]
[http://dx.doi.org/10.1371/journal.pone.0054692] [PMID: 23365678]
[http://dx.doi.org/10.1172/JCI16885] [PMID: 12843127]
[http://dx.doi.org/10.1007/s00213-016-4209-x] [PMID: 26809458]
[http://dx.doi.org/10.1021/jm0600592] [PMID: 16821775]
[http://dx.doi.org/10.1016/j.cell.2007.08.036] [PMID: 17981125]
[http://dx.doi.org/10.1016/j.nucmedbio.2016.08.018] [PMID: 27673755]
[http://dx.doi.org/10.1016/j.nucmedbio.2011.03.006] [PMID: 21982574]
[http://dx.doi.org/10.1016/j.tibs.2003.12.004] [PMID: 15102436]
[http://dx.doi.org/10.1038/labinvest.2011.200] [PMID: 22249311]
[http://dx.doi.org/10.1007/s00125-007-0914-7] [PMID: 18219478]
[PMID: 11829314]
[http://dx.doi.org/10.2337/diabetes.52.3.588] [PMID: 12606497]
[http://dx.doi.org/10.32607/20758251-2013-5-3-84-91] [PMID: 24303204]
[http://dx.doi.org/10.1073/pnas.95.13.7784] [PMID: 9636228]
[http://dx.doi.org/10.1007/s10517-009-0624-x] [PMID: 19902093]
[http://dx.doi.org/10.1007/978-3-319-50174-1_10] [PMID: 28315269]
[http://dx.doi.org/10.1038/s41598-019-53413-w] [PMID: 31745133]
[PMID: 19334503]
[http://dx.doi.org/10.1111/jnc.13756] [PMID: 27488244]
[http://dx.doi.org/10.1007/s11064-015-1670-6] [PMID: 26216050]
[http://dx.doi.org/10.1111/bdi.12449] [PMID: 27882645]
[http://dx.doi.org/10.1179/1743132813Y.0000000209] [PMID: 23622737]
[http://dx.doi.org/10.1155/2011/862708] [PMID: 21738870]