OpenLB
Open Library of Bioscience
Advanced Search
Clinical epigenetics
Jun 11, 2024;16 (1): 78.

Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.

Kukkala Kiran Kumar, Elhadi Husein Aburawi, Milos Ljubisavljevic, Melvin Khee Shing Leow, Xu Feng, Suraiya Anjum Ansari, Bright Starling Emerald
Author Information
  1. Kukkala Kiran Kumar: Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 15551, Al Ain, Abu Dhabi, United Arab Emirates.
  2. Elhadi Husein Aburawi: Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
  3. Milos Ljubisavljevic: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
  4. Melvin Khee Shing Leow: LKC School of Medicine, Nanyang Technological University, Singapore, Singapore.
  5. Xu Feng: Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore, Singapore.
  6. Suraiya Anjum Ansari: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
  7. Bright Starling Emerald: Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 15551, Al Ain, Abu Dhabi, United Arab Emirates. bsemerald@uaeu.ac.ae.
PMID: 38862980 DOI: 10.1186/s13148-024-01692-0

Abstract

Diabetes mellitus is a chronic disease that impairs metabolism, and its prevalence has reached an epidemic proportion globally. Most people affected are with type 2 diabetes mellitus (T2DM), which is caused by a decline in the numbers or functioning of pancreatic endocrine islet cells, specifically the ��-cells that release insulin in sufficient quantity to overcome any insulin resistance of the metabolic tissues. Genetic and epigenetic factors have been implicated as the main contributors to the T2DM. Epigenetic modifiers, histone deacetylases (HDACs), are enzymes that remove acetyl groups from histones and play an important role in a variety of molecular processes, including pancreatic cell destiny, insulin release, insulin production, insulin signalling, and glucose metabolism. HDACs also govern other regulatory processes related to diabetes, such as oxidative stress, inflammation, apoptosis, and fibrosis, revealed by network and functional analysis. This review explains the current understanding of the function of HDACs in diabetic pathophysiology, the inhibitory role of various HDAC inhibitors (HDACi), and their functional importance as biomarkers and possible therapeutic targets for T2DM. While their role in T2DM is still emerging, a better understanding of the role of HDACi may be relevant in improving insulin sensitivity, protecting ��-cells and reducing T2DM-associated complications, among others.

Keywords

Diabetes mellitus Functional analysis HDAC inhibitors HDACs Insulin Pancreatic ��-cells

References

  1. Biomed Pharmacother. 2019 Jan;109:921-929 [PMID: 30551546]
  2. Hum Cell. 2020 Jan;33(1):1-9 [PMID: 31755075]
  3. Nature. 2007 Nov 29;450(7170):712-6 [PMID: 18046409]
  4. FASEB J. 2017 Jul;31(7):3138-3149 [PMID: 28386046]
  5. Nutr Diabetes. 2019 Mar 19;9(1):11 [PMID: 30890694]
  6. Elife. 2021 Nov 05;10: [PMID: 34738906]
  7. EMBO Rep. 2019 Aug;20(8):e48216 [PMID: 31264358]
  8. Immunol Cell Biol. 2012 Jan;90(1):39-46 [PMID: 22083525]
  9. Cell. 2006 Sep 8;126(5):837-9 [PMID: 16959562]
  10. Cell. 2007 Feb 23;128(4):693-705 [PMID: 17320507]
  11. Diabetes Metab. 2005 Dec;31(6):527-32 [PMID: 16357800]
  12. Nat Commun. 2021 Jun 3;12(1):3320 [PMID: 34083525]
  13. Chonnam Med J. 2016 Jan;52(1):1-11 [PMID: 26865995]
  14. Mol Cell. 2017 May 4;66(3):332-344.e4 [PMID: 28475869]
  15. Cell Rep. 2018 Jul 3;24(1):209-223.e6 [PMID: 29972782]
  16. Oxid Med Cell Longev. 2022 Oct 3;2022:1231970 [PMID: 36225175]
  17. FASEB J. 2011 May;25(5):1664-79 [PMID: 21321189]
  18. Diabetes. 2001 Mar;50(3):593-600 [PMID: 11246879]
  19. Diabetes. 2013 Oct;62(10):3500-13 [PMID: 23884882]
  20. Cell Metab. 2017 Apr 4;25(4):838-855.e15 [PMID: 28380376]
  21. Exp Clin Endocrinol Diabetes. 2020 Oct;128(10):663-666 [PMID: 31546272]
  22. Nat Genet. 2022 Nov;54(11):1721-1735 [PMID: 36347944]
  23. Cell Death Dis. 2019 Jan 25;10(2):66 [PMID: 30683850]
  24. Acta Diabetol. 2018 Dec;55(12):1231-1235 [PMID: 30088095]
  25. J Diabetes Res. 2020 Mar 23;2020:1080152 [PMID: 32280711]
  26. Diabetes. 2013 Mar;62(3):685-7 [PMID: 23431009]
  27. Gut. 2023 Mar;72(3):472-483 [PMID: 35580962]
  28. Physiol Rev. 2018 Oct 1;98(4):2133-2223 [PMID: 30067154]
  29. Commun Biol. 2023 Jun 13;6(1):637 [PMID: 37311905]
  30. FEBS J. 2022 May;289(10):2771-2792 [PMID: 33891374]
  31. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1711-6 [PMID: 12578979]
  32. EBioMedicine. 2018 Jul;33:157-168 [PMID: 29958910]
  33. Nature. 2022 May;605(7908):166-171 [PMID: 35477757]
  34. Diabetologia. 2007 Apr;50(4):752-63 [PMID: 17268797]
  35. J Cell Mol Med. 2008 Sep-Oct;12(5A):1571-83 [PMID: 18053091]
  36. Diabetes. 2015 Sep;64(9):3081-92 [PMID: 25948682]
  37. J Biol Chem. 2011 Mar 11;286(10):8338-8348 [PMID: 21196578]
  38. Nature. 2001 Dec 13;414(6865):799-806 [PMID: 11742412]
  39. Nat Commun. 2019 Oct 28;10(1):4905 [PMID: 31659167]
  40. Biochem Biophys Res Commun. 2011 Jan 7;404(1):166-72 [PMID: 21108932]
  41. Cold Spring Harb Perspect Biol. 2014 Apr 01;6(4):a018713 [PMID: 24691964]
  42. J Endocrinol Invest. 2016 Jan;39(1):83-91 [PMID: 26062521]
  43. Bioessays. 2009 Oct;31(10):1050-61 [PMID: 19722182]
  44. EMBO Mol Med. 2019 Sep;11(9):e9854 [PMID: 31368626]
  45. Mol Genet Metab. 2011 Apr;102(4):453-60 [PMID: 21236713]
  46. N Engl J Med. 1993 Mar 11;328(10):697-702 [PMID: 8433729]
  47. J Cell Biol. 2019 Mar 4;218(3):855-870 [PMID: 30792230]
  48. Diabetologia. 2007 Apr;50(4):779-89 [PMID: 17265033]
  49. Cell Metab. 2007 Oct;6(4):307-19 [PMID: 17908559]
  50. PLoS One. 2017 Sep 8;12(9):e0184435 [PMID: 28886131]
  51. Nature. 1996 Dec 5;384(6608):458-60 [PMID: 8945471]
  52. Diabetes. 2014 Jan;63(1):176-87 [PMID: 24101673]
  53. Eur J Pharmacol. 2018 Jan 5;818:371-380 [PMID: 29128366]
  54. Diabetes. 2011 Nov;60(11):2691-700 [PMID: 21896928]
  55. Sci Rep. 2017 Dec;7(1):7 [PMID: 28127057]
  56. Islets. 2023 Dec 31;15(1):2219105 [PMID: 37265106]
  57. Cell Metab. 2005 Sep;2(3):153-63 [PMID: 16154098]
  58. J Clin Invest. 2014 Jan;124(1):30-9 [PMID: 24382387]
  59. Elife. 2021 Oct 08;10: [PMID: 34622775]
  60. Mol Metab. 2016 Nov 22;6(1):30-37 [PMID: 28123935]
  61. Nat Commun. 2017 Jul 31;8(1):162 [PMID: 28757615]
  62. Nat Commun. 2022 Feb 28;13(1):1074 [PMID: 35228549]
  63. Annu Rev Biochem. 2001;70:81-120 [PMID: 11395403]
  64. Mol Med. 2011 May-Jun;17(5-6):369-77 [PMID: 21193899]
  65. J Endocrinol. 2017 Jan;232(1):71-83 [PMID: 27799462]
  66. Mol Metab. 2022 Jun;60:101493 [PMID: 35398277]
  67. Proc Natl Acad Sci U S A. 2019 Mar 19;116(12):5487-5492 [PMID: 30819897]
  68. Cell Metab. 2007 Oct;6(4):247-9 [PMID: 17908551]
  69. Adv Clin Chem. 2021;104:151-231 [PMID: 34462055]
  70. Am J Physiol Endocrinol Metab. 2020 Oct 1;319(4):E805-E813 [PMID: 32865009]
  71. Nat Rev Dis Primers. 2023 Mar 9;9(1):12 [PMID: 36894549]
  72. Nat Commun. 2023 Jul 18;14(1):4296 [PMID: 37463878]
  73. Diabetes. 2008 Apr;57(4):860-7 [PMID: 18184930]
  74. Nat Rev Mol Cell Biol. 2007 Apr;8(4):284-95 [PMID: 17380162]
  75. Eur Rev Med Pharmacol Sci. 2017 Mar;21(5):1091-1098 [PMID: 28338182]
  76. Diabetes. 2009 Feb;58(2):344-51 [PMID: 19008341]
  77. PLoS One. 2018 Sep 27;13(9):e0203713 [PMID: 30260972]
  78. Cell Death Discov. 2023 Apr 18;9(1):131 [PMID: 37072432]
  79. Theranostics. 2021 Mar 4;11(10):4825-4838 [PMID: 33754030]
  80. J Endocrinol. 2016 Nov;231(2):159-165 [PMID: 27601447]
  81. Nat Med. 2012 Jun;18(6):934-42 [PMID: 22561686]
  82. EMBO Rep. 2016 Jun;17(6):811-22 [PMID: 27113762]
  83. Diabetologia. 2018 Apr;61(4):906-918 [PMID: 29322219]
  84. Cell. 2009 Jan 9;136(1):62-74 [PMID: 19135889]
  85. Cell. 2001 Oct 19;107(2):149-59 [PMID: 11672523]
  86. Chem Biol Interact. 2014 Apr 25;213:1-12 [PMID: 24530320]
  87. J Biol Chem. 2009 Jan 9;284(2):759-65 [PMID: 19004825]
  88. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1055-9 [PMID: 24395784]
  89. J Biol Chem. 2004 Dec 24;279(52):54241-7 [PMID: 15496408]
  90. J Diabetes Complications. 2023 Sep;37(9):108566 [PMID: 37536118]
  91. Front Endocrinol (Lausanne). 2021 Sep 24;12:725131 [PMID: 34630329]
  92. Cardiovasc Diabetol. 2013 Jul 12;12:103 [PMID: 23849767]
  93. J Biol Chem. 2007 Jun 29;282(26):19052-61 [PMID: 17412698]
  94. J Cell Biochem. 2019 Oct;120(10):16445-16451 [PMID: 31237015]
  95. Mol Cell Biol. 2008 Oct;28(20):6373-83 [PMID: 18710955]
  96. Cell Metab. 2020 Jan 7;31(1):131-147.e11 [PMID: 31813822]
  97. Nature. 2004 Nov 11;432(7014):226-30 [PMID: 15538371]
  98. EMBO J. 2014 Jun 17;33(12):1287-8 [PMID: 24825350]
  99. Cell Res. 2011 Mar;21(3):381-95 [PMID: 21321607]
  100. Diabetes. 2011 Dec;60(12):3217-22 [PMID: 22013015]
  101. Diabetes. 2010 Mar;59(3):733-40 [PMID: 20009086]
  102. Clin Epigenetics. 2016 Nov 24;8:125 [PMID: 27904654]
  103. J Biol Chem. 2011 Sep 2;286(35):30561-30570 [PMID: 21757760]
  104. Future Oncol. 2017 Jun;13(13):1137-1148 [PMID: 28326839]
  105. Curr Diab Rep. 2021 Apr 18;21(6):18 [PMID: 33866450]
  106. Nat Commun. 2022 Jul 25;13(1):4291 [PMID: 35879296]
  107. Endocrinology. 2021 Jan 1;162(1): [PMID: 32455427]
  108. J Interferon Cytokine Res. 2015 Jan;35(1):63-70 [PMID: 25062500]
  109. Nat Rev Endocrinol. 2022 Sep;18(9):540-557 [PMID: 35585199]
  110. Cell Rep. 2019 Oct 15;29(3):781-784 [PMID: 31618644]
  111. Mol Med Rep. 2020 Nov;22(5):4041-4047 [PMID: 32901855]
  112. Epilepsia. 2015 Nov;56(11):e172-5 [PMID: 26250143]
  113. Sci Rep. 2016 Jul 26;6:30321 [PMID: 27457971]
  114. EBioMedicine. 2017 Apr;18:128-138 [PMID: 28396013]
  115. Bioorg Med Chem Lett. 2020 Aug 15;30(16):127215 [PMID: 32631504]
  116. Am J Physiol Endocrinol Metab. 2018 Aug 1;315(2):E150-E162 [PMID: 29634312]
  117. Eur J Pharmacol. 2023 Jun 15;949:175728 [PMID: 37062501]
  118. Cell Metab. 2005 Aug;2(2):105-17 [PMID: 16098828]
  119. Chem Biol. 2010 May 28;17(5):471-82 [PMID: 20534345]
  120. Medicine (Baltimore). 2022 Dec 23;101(51):e32461 [PMID: 36595822]
  121. Front Endocrinol (Lausanne). 2022 Jul 13;13:881256 [PMID: 35909530]
  122. EMBO J. 2012 May 16;31(10):2275-95 [PMID: 22510882]
  123. Anal Chem. 2022 Aug 2;94(30):10705-10714 [PMID: 35862615]
  124. Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14460-5 [PMID: 19667185]
  125. Cell Death Dis. 2020 Oct 2;11(10):821 [PMID: 33009367]
  126. Cell Metab. 2005 Aug;2(2):80-2 [PMID: 16098824]
  127. Sci Rep. 2015 Dec 01;5:17395 [PMID: 26620281]
  128. J Diabetes Clin Res. 2019;1(1):5-23 [PMID: 32432227]
  129. J Biol Chem. 2007 Nov 16;282(46):33583-33592 [PMID: 17715127]
  130. Environ Toxicol Pharmacol. 2018 Dec;64:112-121 [PMID: 30342372]
  131. Biomed Pharmacother. 2020 Aug;128:110226 [PMID: 32460191]
  132. Endocr Rev. 2016 Jun;37(3):190-222 [PMID: 27035557]
  133. Diabetes. 2012 Feb;61(2):513-23 [PMID: 22210316]
  134. Nucleic Acids Res. 2018 Dec 14;46(22):11776-11788 [PMID: 30321390]
  135. Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14608-13 [PMID: 21873205]
  136. Mol Metab. 2017 Oct;6(10):1264-1273 [PMID: 29031725]
  137. Cell Commun Signal. 2021 May 25;19(1):61 [PMID: 34034759]
  138. Nat Commun. 2021 May 28;12(1):3208 [PMID: 34050173]
  139. J Diabetes Res. 2014;2014:195739 [PMID: 25610877]
  140. Nat Metab. 2022 Jan;4(1):44-59 [PMID: 35039672]
  141. J Biol Chem. 2014 Feb 28;289(9):6054-66 [PMID: 24446434]
  142. J Biol Chem. 2023 Aug;299(8):105045 [PMID: 37451484]
  143. Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):370-377 [PMID: 35538036]
  144. Mol Med. 2022 Jul 16;28(1):81 [PMID: 35842608]
  145. Diabetes Care. 2011 Aug;34(8):1878-84 [PMID: 21788644]
  146. Front Endocrinol (Lausanne). 2021 Jul 22;12:679655 [PMID: 34367065]
  147. Cardiovasc Diabetol. 2018 Aug 31;17(1):122 [PMID: 30170598]
  148. J Neurochem. 2016 May;137(3):371-83 [PMID: 26896748]
  149. Nat Med. 2024 Apr;30(4):1065-1074 [PMID: 38443691]
  150. Metabolism. 2008 Jul;57(7):986-98 [PMID: 18555842]
  151. Cell Physiol Biochem. 2018;49(3):996-1006 [PMID: 30196291]
  152. Nat Genet. 2011 Dec 11;44(1):20-22 [PMID: 22158542]
  153. Diabetes. 2010 Sep;59(9):2326-31 [PMID: 20573748]
  154. Mol Cell. 2015 Jul 16;59(2):321-32 [PMID: 26073543]
  155. Diabetologia. 2016 Jan;59(1):151-160 [PMID: 26471901]
  156. Mol Metab. 2015 Sep 25;4(11):846-56 [PMID: 26629408]
  157. Chem Biol. 2012 Jun 22;19(6):669-73 [PMID: 22726680]
  158. Epilepsy Res. 2003 Jun-Jul;55(1-2):53-8 [PMID: 12948616]
  159. EMBO J. 2004 Feb 25;23(4):950-8 [PMID: 14765107]
  160. Science. 2011 May 20;332(6032):977-80 [PMID: 21596991]
  161. Nat Commun. 2015 May 12;6:7078 [PMID: 25963408]
  162. Protein Cell. 2019 Jun;10(6):436-449 [PMID: 30324491]
  163. Mol Genet Genomic Med. 2019 May;7(5):e602 [PMID: 30968599]
  164. Drug Discov Today. 2010 Sep;15(17-18):757-65 [PMID: 20692359]
  165. J Neuroinflammation. 2019 May 17;16(1):103 [PMID: 31101061]
  166. Cell. 2006 Dec 15;127(6):1091-3 [PMID: 17174885]
  167. Diabetes. 2017 Oct;66(10):2659-2668 [PMID: 28607107]
  168. Front Endocrinol (Lausanne). 2019 Mar 27;10:187 [PMID: 30972029]
  169. Diabetologia. 2017 Jan;60(1):116-125 [PMID: 27796421]
  170. Lancet Oncol. 2011 Dec;12(13):1222-8 [PMID: 22033282]
  171. EMBO Rep. 2018 Dec;19(12): [PMID: 30420520]
  172. Am J Hum Genet. 2015 Jul 2;97(1):177-85 [PMID: 26073777]
  173. Theranostics. 2020 Jun 5;10(16):7351-7368 [PMID: 32641996]
  174. Nat Genet. 1997 Oct;17(2):138-9 [PMID: 9326926]
  175. Sci Adv. 2017 Oct 27;3(10):e1700957 [PMID: 29098179]
  176. Cell. 2011 May 13;145(4):607-21 [PMID: 21565617]
  177. Exp Mol Med. 2016 Mar 11;48:e219 [PMID: 26964835]
  178. Pediatr Diabetes. 2022 Aug;23(5):597-603 [PMID: 35689450]
  179. Mol Cancer. 2020 Jan 7;19(1):5 [PMID: 31910827]
  180. Diabetes. 2011 Dec;60(12):3197-207 [PMID: 21998399]
  181. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6509-6520 [PMID: 32152128]
  182. Cell Transplant. 2011;20(9):1321-32 [PMID: 21294957]
  183. J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2322-e2333 [PMID: 33417713]
  184. Diabetes. 2011 Nov;60(11):2861-71 [PMID: 21953612]
  185. Mol Cell Biol. 2003 Feb;23(3):1025-33 [PMID: 12529406]
  186. Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12861-6 [PMID: 17646659]
  187. Diabetologia. 2012 Sep;55(9):2421-31 [PMID: 22772764]
  188. Curr Opin Chem Biol. 1997 Oct;1(3):300-8 [PMID: 9667866]
  189. Curr Vasc Pharmacol. 2020;18(2):110-116 [PMID: 30961498]
  190. Mol Cell. 2012 Dec 28;48(6):900-13 [PMID: 23142079]
  191. Diabetologia. 2013 Jan;56(1):162-72 [PMID: 23070058]
  192. Cell. 2006 Sep 8;126(5):941-54 [PMID: 16959573]
  193. Cell Commun Signal. 2021 Mar 18;19(1):35 [PMID: 33736642]
  194. Cell Metab. 2020 Mar 3;31(3):580-591.e5 [PMID: 32032542]
  195. J Med Chem. 2018 Dec 13;61(23):10922-10928 [PMID: 30395713]
  196. J Clin Lab Anal. 2022 Aug;36(8):e24583 [PMID: 35778952]
  197. Nat Commun. 2017 Nov 30;8(1):1878 [PMID: 29192248]
  198. Diabetologia. 2022 Oct;65(10):1601-1612 [PMID: 35867127]
  199. Development. 2019 Jul 24;146(14): [PMID: 31142539]
  200. EMBO Rep. 2017 Apr;18(4):645-657 [PMID: 28270525]
  201. Nat Rev Drug Discov. 2007 Jan;6(1):21-2 [PMID: 17269160]
  202. Diabetologia. 2010 Dec;53(12):2569-78 [PMID: 20878317]
  203. Biochem Pharmacol. 2007 Sep 1;74(5):659-71 [PMID: 17498667]
  204. Cell. 2010 Jan 22;140(2):280-93 [PMID: 20141841]
  205. J Med Chem. 2018 Mar 22;61(6):2460-2471 [PMID: 29494161]
  206. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10684-9 [PMID: 25009184]
  207. Diabetes. 2014 Aug;63(8):2888-94 [PMID: 24696446]
  208. Trends Genet. 2010 Nov;26(11):476-83 [PMID: 20832136]
  209. Nature. 1997 Sep 11;389(6647):194-8 [PMID: 9296499]
  210. Front Endocrinol (Lausanne). 2023 Dec 19;14:1301093 [PMID: 38179301]
  211. Diabetologia. 2013 May;56(5):1068-77 [PMID: 23397292]
  212. J Biol Chem. 2005 Jun 10;280(23):21797-803 [PMID: 15831498]
  213. Biosci Rep. 2020 Sep 30;40(9): [PMID: 32815547]
  214. Clin Exp Immunol. 2013 Jun;172(3):375-82 [PMID: 23600825]

Grants

  1. ASPIRE Precision Medicine Research Institute Abu Dhabi (VRI-20-10)/ASPIRE, the technology program management pillar of Abu Dhabi's Advanced Technology Research Council (ATRC)
  2. UAEU-IIT collaborative grant 31M492/12M053/United Arab Emirates University
  3. Grant 21R110/Zayed Bin Sultan Charitable and Humanitarian Foundation (ZCHF)
  4. Faculty grant 3IM279, 12M086/College of Medicine and Health Sciences, United Arab Emirates University

MeSH Term

Humans
Diabetes Mellitus, Type 2
Histone Deacetylases
Histone Deacetylase Inhibitors
Epigenesis, Genetic
Insulin Resistance
Insulin-Secreting Cells
Animals
Oxidative Stress
Insulin

Chemicals

Histone Deacetylases
Histone Deacetylase Inhibitors
Insulin
Journal Article Review

Word Cloud

Created with Highcharts 10.0.0insulinT2DMHDACsrolemellitusdiabetes��-cellsDiabetesmetabolismtype2pancreaticreleasehistonedeacetylasesprocessesfunctionalanalysisunderstandingHDACinhibitorsHDACitherapeuticchronicdiseaseimpairsprevalencereachedepidemicproportiongloballypeopleaffectedcauseddeclinenumbersfunctioningendocrineisletcellsspecificallysufficientquantityovercomeresistancemetabolictissuesGeneticepigeneticfactorsimplicatedmaincontributorsEpigeneticmodifiersenzymesremoveacetylgroupshistonesplayimportantvarietymolecularincludingcelldestinyproductionsignallingglucosealsogovernregulatoryrelatedoxidativestressinflammationapoptosisfibrosisrevealednetworkreviewexplainscurrentfunctiondiabeticpathophysiologyinhibitoryvariousimportancebiomarkerspossibletargetsstillemergingbettermayrelevantimprovingsensitivityprotectingreducingT2DM-associatedcomplicationsamongothersExploringmellitus:pathophysiologicalinsightsavenuesFunctionalInsulinPancreatic

Similar Articles

Cited By