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Role of miRNAs in the pathogenesis of T2DM, insulin secretion, insulin resistance, and β cell dysfunction: the story so far

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Abstract

Diabetes, the most common endocrine disorder, also known as a silent killer disease, is characterized by uncontrolled hyperglycemia. According to the International Diabetes Federation, there were 451 million people with diabetes mellitus worldwide in 2017. It is a multifactorial syndrome caused by genetic as well as environmental factors. Noncoding RNAs, especially the miRNAs, play a significant role in the development as well as the progression of the disease. This is on account of insulin resistance or defects in β cell function. Various miRNAs including miR-7, miR-9, miR-16, miR-27, miR-24, miR-29, miR-124a, miR-135, miR-130a, miR-144, miR-181a, and miR-375 and many more have been associated with insulin resistance and other pathogenic conditions leading to the development of the disease. These miRNAs play significant roles in various pathways underlying insulin resistance such as PI3K, AKT/GSK, and mTOR. The main target genes of these miRNAs are FOXO1, FOXA2, STAT3, and PTEN. The miRNAs carry out important functions in insulin target tissues like the adipose tissue, liver, and muscle. MiRNAs miR-9, miR-375, and miR-124a, are also associated with the secretion of insulin from pancreatic cells. There is an interplay between the miRNAs and pancreatic cell growth, especially the miRNAs affecting development and proliferation of these cells. Most of the miRNAs target more than one gene which not only justifies their use as biomarkers but also their therapeutic potential. The current review has been compiled with an aim to discuss the role of various miRNAs involved in various pathogenic mechanisms including insulin resistance, insulin secretion, and the β cell dysfunction.

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References

  1. Agarwal P, Srivastava R, Srivastava AK, Ali S, Datta M (2013) miR-135a targets IRS2 and regulates insulin signaling and glucose uptake in the diabetic gastrocnemius skeletal muscle. Biochim Biophys Acta (BBA) Mol Basis Dis 1832:1294–1303

    CAS  Google Scholar 

  2. Ambros V, Lee RC (2004) Identification of microRNAs and other tiny noncoding RNAs by cDNA cloning. In: RNA Interference, Editing, and Modification. Springer, pp 131–158

  3. Bagge A, Clausen TR, Larsen S, Ladefoged M, Rosenstierne MW, Larsen L, Vang O, Nielsen JH, Dalgaard LT (2012) MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion. Biochem Biophys Res Commun 426:266–272

    CAS  PubMed  Google Scholar 

  4. Bao L, Fu X, Si M, Wang Y, Ma R, Ren X, Lv H (2015) MicroRNA-185 targets SOCS3 to inhibit beta-cell dysfunction in diabetes. PloS one 10:e0116067

    PubMed  PubMed Central  Google Scholar 

  5. Baroukh N, Ravier MA, Loder MK, Hill EV, Bounacer A, Scharfmann R, Rutter GA, Van Obberghen E (2007) MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic β-cell lines. J Biol Chem 282:19575–19588

    CAS  PubMed  Google Scholar 

  6. Bijkerk R, Esguerra JL, Ellenbroek JH, Au YW, Hanegraaf MA, de Koning EJ, Eliasson L, van Zonneveld AJ (2019) In vivo silencing of microRNA-132 reduces blood glucose and improves insulin secretion. Nucleic Acid Ther 29:67–72

    CAS  PubMed  Google Scholar 

  7. Dávalos A, Goedeke L, Smibert P, Ramírez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC (2011) miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci 108:9232–9237

    PubMed  Google Scholar 

  8. Davies MJ, D’Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB (2018) Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 61:2461–2498

    PubMed  Google Scholar 

  9. Dou L, Zhao T, Wang L, Huang X, Jiao J, Gao D, Zhang H, Shen T, Man Y, Wang S (2013) miR-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes. J Biol Chem 288:22596–22606

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Fernandez-Valverde SL, Taft RJ, Mattick JS (2011) MicroRNAs in β-cell biology, insulin resistance, diabetes and its complications. Diabetes. 60:1825–1831

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Foley NH, OˈNeill LA (2012) miR-107: a Toll-like receptor-regulated miRNA dysregulated in obesity and type II diabetes. J Leukocyte Biol 92:521–527

    CAS  PubMed  Google Scholar 

  12. Guay C, Roggli E, Nesca V, Jacovetti C, Regazzi R (2011) Diabetes mellitus, a microRNA-related disease? Transl Res 157:253–264

    CAS  PubMed  Google Scholar 

  13. Guay C, Jacovetti C, Nesca V, Motterle A, Tugay K, Regazzi R (2012) Emerging roles of non-coding RNAs in pancreatic β-cell function and dysfunction. Diabetes Obes Metab 14:12–21

    CAS  PubMed  Google Scholar 

  14. He A, Zhu L, Gupta N, Chang Y, Fang F (2007) Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Mol Endocrinol 21:2785–2794

    CAS  PubMed  Google Scholar 

  15. He Y, Ding Y, Liang B, Lin J, Kim T-K, Yu H, Hang H, Wang K (2017) A systematic study of dysregulated microRNA in type 2 diabetes mellitus. Int J Mol Sci 18:456

    PubMed Central  Google Scholar 

  16. Hennessy E, Clynes M, Jeppesen PB, O’Driscoll L (2010) Identification of microRNAs with a role in glucose stimulated insulin secretion by expression profiling of MIN6 cells. Biochem Biophys Res Commun 396:457–462

    CAS  PubMed  Google Scholar 

  17. Herrera BM, Lockstone HE, Taylor JM, Wills QF, Kaisaki PJ, Barrett A, Camps C, Fernandez C, Ragoussis J, Gauguier D (2009) MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes. BMC Med Genomics 2:54

    PubMed  PubMed Central  Google Scholar 

  18. Herrera B, Lockstone H, Taylor J, Ria M, Barrett A, Collins S, Kaisaki P, Argoud K, Fernandez C, Travers M (2010) Global microRNA expression profiles in insulin target tissues in a spontaneous rat model of type 2 diabetes. Diabetologia. 53:1099–1109

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Honardoost M, Keramati F, Arefian E, Mohammadi Yeganeh S, Soleimani M (2019) Network of three specific microRNAs influence type 2 diabetes through inducing insulin resistance in muscle cell lines. J Cell Biochem 120:1532–1538

    CAS  Google Scholar 

  20. Hu X, Chi L, Zhang W, Bai T, Zhao W, Feng Z, Tian H (2015) Down-regulation of the miR-543 alleviates insulin resistance through targeting the SIRT1. Biochem Biophys Res Commun 468:781–787

    CAS  PubMed  Google Scholar 

  21. Hu D, Wang Y, Zhang H, Kong D (2018) Identification of miR-9 as a negative factor of insulin secretion from beta cells. J Physiol Biochem 74:291–299

    CAS  PubMed  Google Scholar 

  22. Hung Y-H, Kanke M, Kurtz CL, Cubitt R, Bunaciu RP, Miao J, Zhou L, Graham JL, Hussain MM, Havel P (2019) Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice. Physiol Genomics 51:379–389

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Jacovetti C, Abderrahmani A, Parnaud G, Jonas J-C, Peyot M-L, Cornu M, Laybutt R, Meugnier E, Rome S, Thorens B (2012) MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity. J Clin Investig 122:3541–3551

    CAS  PubMed  Google Scholar 

  24. Jacovetti C, Jimenez V, Ayuso E, Laybutt R, Peyot M-L, Prentki M, Bosch F, Regazzi R (2015) Contribution of Intronic miR-338–3p and its hosting gene AATK to compensatory β-cell mass expansion. Mol Endocrinol 29:693–702

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Jalabert A, Vial G, Guay C, Wiklander OP, Nordin JZ, Aswad H, Forterre A, Meugnier E, Pesenti S, Regazzi R (2016) Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice. Diabetologia. 59:1049–1058

    CAS  PubMed  Google Scholar 

  26. Jiao Y, Zhu M, Mao X, Long M, Du X, Wu Y, Abudureyimu K, Zhang C, Wang Y, Tao Y (2015) MicroRNA-130a expression is decreased in Xinjiang Uygur patients with type 2 diabetes mellitus, Am J Transl Res. 7:1984

  27. Joglekar MV, Parekh VS, Mehta S, Bhonde RR, Hardikar AA (2007) MicroRNA profiling of developing and regenerating pancreas reveal post-transcriptional regulation of neurogenin3. Dev Biol 311:603–612

    CAS  PubMed  Google Scholar 

  28. Joglekar MV, Joglekar VM, Hardikar AA (2009) Expression of islet-specific microRNAs during human pancreatic development. Gene Express Patterns 9:109–113

    CAS  Google Scholar 

  29. Jordan SD, Krüger M, Willmes DM, Redemann N, Wunderlich FT, Brönneke HS, Merkwirth C, Kashkar H, Olkkonen VM, Böttger T (2011) Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism. Nat Cell Biol 13:434

    CAS  PubMed  Google Scholar 

  30. Karolina DS, Armugam A, Tavintharan S, Wong MT, Lim SC, Sum CF, Jeyaseelan K (2011) MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus. PloS one 6:e22839

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Katayama M, Wiklander OP, Fritz T, Caidahl K, El-Andaloussi S, Zierath JR, Krook A (2019) Circulating exosomal miR-20b-5p is elevated in type 2 diabetes and could impair insulin action in human skeletal muscle. Diabetes. 68:515–526

    CAS  PubMed  Google Scholar 

  32. Kim J-W, You Y-H, Jung S, Suh-Kim H, Lee I-K, Cho J-H, Yoon K-H (2013) miRNA-30a-5p-mediated silencing of Beta2/NeuroD expression is an important initial event of glucotoxicity-induced beta cell dysfunction in rodent models. Diabetologia. 56:847–855

    CAS  PubMed  Google Scholar 

  33. Klein D, Misawa R, Bravo-Egana V, Vargas N, Rosero S, Piroso J, Ichii H, Umland O, Zhijie J, Tsinoremas N (2013) MicroRNA expression in alpha and beta cells of human pancreatic islets. PloS one 8:e55064

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Kurtz CL, Peck BC, Fannin EE, Beysen C, Miao J, Landstreet SR, Ding S, Turaga V, Lund PK, Turner S (2014) MicroRNA-29 fine-tunes the expression of key FOXA2-activated lipid metabolism genes and is dysregulated in animal models of insulin resistance and diabetes. Diabetes. 63:3141–3148

    PubMed  PubMed Central  Google Scholar 

  35. Lahmy R, Soleimani M, Sanati MH, Behmanesh M, Kouhkan F, Mobarra N (2014) MiRNA-375 promotes beta pancreatic differentiation in human induced pluripotent stem (hiPS) cells. Mol Biol Rep 41:2055–2066

    CAS  PubMed  Google Scholar 

  36. Lang H, Xiang Y, Lin N, Ai Z, You Z, Xiao J, Liu D, Yang Y (2018) Identification of a panel of MiRNAs as positive regulators of insulin release in pancreatic Β-Cells. Cell Physiol Biochem 48:185–193

    CAS  PubMed  Google Scholar 

  37. Latouche C, Natoli A, Reddy-Luthmoodoo M, Heywood SE, Armitage JA, Kingwell BA (2016) MicroRNA-194 modulates glucose metabolism and its skeletal muscle expression is reduced in diabetes. PloS one 11:e0155108

    PubMed  PubMed Central  Google Scholar 

  38. Latreille M, Hausser J, Stützer I, Zhang Q, Hastoy B, Gargani S, Kerr-Conte J, Pattou F, Zavolan M, Esguerra JL (2014) MicroRNA-7a regulates pancreatic β cell function. J Clin Investig 124:2722–2735

    CAS  PubMed  Google Scholar 

  39. Lee DE, Brown JL, Rosa ME, Brown LA, Perry RA Jr, Wiggs MP, Nilsson MI, Crouse SF, Fluckey JD, Washington TA (2016) microRNA-16 is downregulated during insulin resistance and controls skeletal muscle protein accretion. J Cell Biochem 117:1775–1787

    CAS  PubMed  Google Scholar 

  40. Li X (2014) MiR-375, a microRNA related to diabetes. Gene. 533:1–4

    CAS  PubMed  Google Scholar 

  41. Li Y, Deng S, Peng J, Wang X, Essandoh K, Mu X, Peng T, Meng Z-X, Fan G-C (2019) MicroRNA-223 is essential for maintaining functional β-cell mass during diabetes through inhibiting both FOXO1 and SOX6 pathways. J Biol Chem:jbc. RA119. 007755

  42. Ling HY, Ou HS, Feng SD, Zhang XY, Tuo QH, Chen LX, Zhu BY, Gao ZP, Tang CK, Yin WD (2009) CHANGES IN microRNA (miR) profile and effects of miR-320 in insulin-resistant 3T3-L1 adipocytes. Clin Exp Pharmacol Physiol 36:e32–e39

    CAS  PubMed  Google Scholar 

  43. Ling H-Y, Hu B, Hu X-B, Zhong J, Qin L, Liu G, Wen G-b, Liao D-F (2012) MiRNA-21 reverses high glucose and high insulin induced insulin resistance in 3T3-L1 adipocytes through targeting phosphatase and tensin homologue. Exp Clin Endocrinol Diabetes 120:553–559

    CAS  PubMed  Google Scholar 

  44. Liu T, Sun Y-C, Cheng P, Shao H-G (2019) Adipose tissue macrophage-derived exosomal miR-29a regulates obesity-associated insulin resistance. Biochem Biophys Res Commun

  45. Locke J, da Silva Xavier G, Dawe H, Rutter G, Harries L (2014) Increased expression of miR-187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion. Diabetologia. 57:122–128

    CAS  PubMed  Google Scholar 

  46. Lovis P, Gattesco S, Regazzi R (2008) Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs. Biol Chem 389:305–312

    CAS  PubMed  Google Scholar 

  47. Luo A, Yan H, Liang J, Du C, Zhao X, Sun L, Chen Y (2017) MicroRNA-21 regulates hepatic glucose metabolism by targeting FOXO1. Gene. 627:194–201

    CAS  PubMed  Google Scholar 

  48. Lynn FC, Skewes-Cox P, Kosaka Y, McManus MT, Harfe BD, German MS (2007) MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes. 56:2938–2945

    CAS  PubMed  Google Scholar 

  49. Mattick JS, Makunin IV (2006) Non-coding RNA. Hum Mol Genet 15:R17–R29

    CAS  PubMed  Google Scholar 

  50. Melkman-Zehavi T, Oren R, Kredo-Russo S, Shapira T, Mandelbaum AD, Rivkin N, Nir T, Lennox KA, Behlke MA, Dor Y (2011) miRNAs control insulin content in pancreatic β-cells via downregulation of transcriptional repressors. EMBO J 30:835–845

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Mohan R, Mao Y, Zhang S, Zhang Y-W, Xu C-R, Gradwohl G, Tang X (2015) Differentially expressed microRNA-483 confers distinct functions in pancreatic β-and α-cells. J Biol Chem 290:19955–19966

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Morita S, Horii T, Kimura M, Hatada I (2013) MiR-184 regulates insulin secretion through repression of Slc25a22. PeerJ. 1:e162

    PubMed  PubMed Central  Google Scholar 

  53. Nesca V, Guay C, Jacovetti C, Menoud V, Peyot M-L, Laybutt DR, Prentki M, Regazzi R (2013) Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes. Diabetologia. 56:2203–2212

    CAS  PubMed  Google Scholar 

  54. Plaisance V, Abderrahmani A, Perret-Menoud V, Jacquemin P, Lemaigre F, Regazzi R (2006) MicroRNA-9 controls the expression of granuphilin/Slp4 and the secretory response of insulin-producing cells. J Biol Chem 281:26932–26942

    CAS  PubMed  Google Scholar 

  55. Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 432:226–230

    CAS  PubMed  Google Scholar 

  56. Poy MN, Hausser J, Trajkovski M, Braun M, Collins S, Rorsman P, Zavolan M, Stoffel M (2009) miR-375 maintains normal pancreatic α-and β-cell mass. Proc Natl Acad Sci 106:5813–5818

    CAS  PubMed  Google Scholar 

  57. Ramachandran D, Roy U, Garg S, Ghosh S, Pathak S, Kolthur-Seetharam U (2011) Sirt1 and mir-9 expression is regulated during glucose-stimulated insulin secretion in pancreatic β-islets. FEBS J 278:1167–1174

    CAS  PubMed  Google Scholar 

  58. Rubie C, Zimmer J, Lammert F, Gross JC, Weber SN, Kruse B, Halajda B, Wagner M, Wagenpfeil S, Glanemann M (2019) MicroRNA-496 and mechanistic target of rapamycin expression are associated with type 2 diabetes mellitus and obesity in elderly people. Ann Nutr Metab 74:279–286

    CAS  PubMed  Google Scholar 

  59. Sebastiani G, Po A, Miele E, Ventriglia G, Ceccarelli E, Bugliani M, Marselli L, Marchetti P, Gulino A, Ferretti E (2015) MicroRNA-124a is hyperexpressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion. Acta Diabetol 52:523–530

    CAS  PubMed  Google Scholar 

  60. Song H, Ding L, Zhang S, Wang W (2018) MiR-29 family members interact with SPARC to regulate glucose metabolism. Biochem Biophys Res Commun 497:667–674

    CAS  PubMed  Google Scholar 

  61. Song Y, Wu L, Li M, Xiong X, Fang Z, Zhou J, Yan G, Chen X, Yang J, Li Y (2019) Down-regulation of MicroRNA-592 in obesity contributes to hyperglycemia and insulin resistance. EBioMedicine. 42:494–503

    PubMed  PubMed Central  Google Scholar 

  62. Soni MS, Rabaglia ME, Bhatnagar S, Shang J, Ilkayeva O, Mynatt R, Zhou Y-P, Schadt EE, Thornberry NA, Muoio DM (2014) Downregulation of carnitine acyl-carnitine translocase by miRNAs 132 and 212 amplifies glucose-stimulated insulin secretion. Diabetes. 63:3805–3814

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Su T, Xiao Y, Xiao Y, Guo Q, Li C, Huang Y, Deng Q, Wen J, Zhou F, Luo X-H (2019) Bone marrow mesenchymal stem cells-derived exosomal MiR-29b-3p regulates aging-associated insulin resistance. ACS nano 13:2450–2462

    CAS  PubMed  Google Scholar 

  64. Sun L-L, Jiang B-G, Li W-T, Zou J-J, Shi Y-Q, Liu Z-M (2011) MicroRNA-15a positively regulates insulin synthesis by inhibiting uncoupling protein-2 expression. Diabetes Res Clin Pract 91:94–100

    CAS  PubMed  Google Scholar 

  65. Sun J, Huang Q, Li S, Meng F, Li X, Gong X (2018) miR-330-5p/Tim-3 axis regulates macrophage M2 polarization and insulin resistance in diabetes mice. Mol Immunol 95:107–113

    CAS  PubMed  Google Scholar 

  66. Talari M, Kapadia B, Kain V, Seshadri S, Prajapati B, Rajput P, Misra P, Parsa KV (2015) MicroRNA-16 modulates macrophage polarization leading to improved insulin sensitivity in myoblasts. Biochimie. 119:16–26

    CAS  PubMed  Google Scholar 

  67. Tang X, Muniappan L, Tang G, Özcan S (2009) Identification of glucose-regulated miRNAs from pancreatic β cells reveals a role for miR-30d in insulin transcription. Rna. 15:287–293

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Trajkovski M, Hausser J, Soutschek J, Bhat B, Akin A, Zavolan M, Heim MH, Stoffel M (2011) MicroRNAs 103 and 107 regulate insulin sensitivity. Nature. 474:649–653

    CAS  PubMed  Google Scholar 

  69. van de Bunt M, Gaulton KJ, Parts L, Moran I, Johnson PR, Lindgren CM, Ferrer J, Gloyn AL, McCarthy MI (2013) The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis. PloS one 8:e55272

    PubMed  PubMed Central  Google Scholar 

  70. Wang Y, Liu J, Liu C, Naji A, Stoffers DA (2013) MicroRNA-7 regulates the mTOR pathway and proliferation in adult pancreatic β-cells. Diabetes. 62:887–895

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Wang X, Wang M, Li H, Lan X, Liu L, Li J, Li Y, Li J, Yi J, Du X (2015) Upregulation of miR-497 induces hepatic insulin resistance in E3 rats with HFD-MetS by targeting insulin receptor. Mol Cell Endocrinol 416:57–69

    CAS  PubMed  Google Scholar 

  72. Wang W, Wang J, Yan M, Jiang J, Bian A (2018) MiRNA-92a protects pancreatic B-cell function by targeting KLF2 in diabetes mellitus. Biochem Biophys Res Commun 500:577–582

    CAS  PubMed  Google Scholar 

  73. Wei R, Yang J, Liu G-q, Gao M-j, Hou W-f, Zhang L, Gao H-w, Liu Y, Chen G-a, Hong T-p (2013) Dynamic expression of microRNAs during the differentiation of human embryonic stem cells into insulin-producing cells. Gene. 518:246–255

    CAS  PubMed  Google Scholar 

  74. Wei S, Zhang M, Yu Y, Xue H, Lan X, Liu S, Hatch G, Chen L (2016) HNF-4α regulated miR-122 contributes to development of gluconeogenesis and lipid metabolism disorders in type 2 diabetic mice and in palmitate-treated HepG2 cells. Eur J Pharmacol 791:254–263

    CAS  PubMed  Google Scholar 

  75. Wen F, Yang Y, Jin D, Sun J, Yu X, Yang Z (2014) MiRNA-145 is involved in the development of resistin-induced insulin resistance in HepG2 cells. Biochem Biophys Res Commun 445:517–523

    CAS  PubMed  Google Scholar 

  76. Williams MD, Mitchell GM (2012) MicroRNAs in insulin resistance and obesity. Exp Diabetes Res 2012:1–8

    Google Scholar 

  77. Xiao F, Yu J, Liu B, Guo Y, Li K, Deng J, Zhang J, Wang C, Chen S, Du Y (2014) A novel function of microRNA 130a-3p in hepatic insulin sensitivity and liver steatosis. Diabetes. 63:2631–2642

    CAS  PubMed  Google Scholar 

  78. Xu L, Li Y, Yin L, Qi Y, Sun H, Sun P, Xu M, Tang Z, Peng J (2018) miR-125a-5p ameliorates hepatic glycolipid metabolism disorder in type 2 diabetes mellitus through targeting of STAT3. Theranostics 8:5593

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Yang W-M, Jeong H-J, Park S-Y, Lee W (2014) Saturated fatty acid-induced miR-195 impairs insulin signaling and glycogen metabolism in HepG2 cells. FEBS Lett 588:3939–3946

    CAS  PubMed  Google Scholar 

  80. Yang WM, Jeong HJ, Park SW, Lee W (2015) Obesity-induced miR-15b is linked causally to the development of insulin resistance through the repression of the insulin receptor in hepatocytes. Mol Nutr Food Res 59:2303–2314

    CAS  PubMed  Google Scholar 

  81. Ying C, Sui-xin L, Kang-ling X, Wen-liang Z, Lei D, Yuan L, Fan Z, Chen Z (2014) MicroRNA-492 reverses high glucose-induced insulin resistance in HUVEC cells through targeting resistin. Molecular and cell Biochem 391:117–125

    Google Scholar 

  82. Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, Ofrecio JM, Wollam J, Hernandez-Carretero A, Fu W (2017) Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell 171:372–384. e12

    CAS  PubMed  Google Scholar 

  83. Yu X, Zhong L (2018) Pioglitazone/microRNA-141/FOXA2: A novel axis in pancreatic β-cells proliferation and insulin secretion. Mol Med Rep 17:7931–7938

    CAS  PubMed  Google Scholar 

  84. Yu Y, Du H, Wei S, Feng L, Li J, Yao F, Zhang M, Hatch GM, Chen L (2018) Adipocyte-derived exosomal MiR-27a induces insulin resistance in skeletal muscle through repression of PPARγ. Theranostics. 8:2171–2188

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Yu C-Y, Yang C-Y, Rui Z-L (2019) MicroRNA-125b-5p improves pancreatic β-cell function through inhibiting JNK signaling pathway by targeting DACT1 in mice with type 2 diabetes mellitus. Life Sci 224:67–75

    CAS  PubMed  Google Scholar 

  86. Zhang Y, Yang L, Gao Y-F, Fan Z-M, Cai X-Y, Liu M-Y, Guo X-R, Gao C-L, Xia Z-K (2013) MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting mitofusin-2. Mol Cell Endocrinol 381:230–240

    CAS  PubMed  Google Scholar 

  87. Zhang D, Li Y, Yao X, Wang H, Zhao L, Jiang H, Yao X, Zhang S, Ye C, Liu W (2016) miR-182 regulates metabolic homeostasis by modulating glucose utilization in muscle. Cell Rep 16:757–768

    PubMed  Google Scholar 

  88. Zhao X, Mohan R, Özcan S, Tang X (2012) MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic β-cells. J Biol Chem 287:31155–31164

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Zhou B, Li C, Qi W, Zhang Y, Zhang F, Wu J, Hu Y, Wu D, Liu Y, Yan T (2012) Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity. Diabetologia. 55:2032–2043

    CAS  PubMed  Google Scholar 

  90. Zhu Y, You W, Wang H, Li Y, Qiao N, Shi Y, Zhang C, Bleich D, Han X (2013) MicroRNA-24/MODY gene regulatory pathway mediates pancreatic β-cell dysfunction. Diabetes. 62:3194–3206

    CAS  PubMed  PubMed Central  Google Scholar 

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Funding

Central University of Punjab, Bathinda, and CSIR (junior research fellowship to Prabhsimran Kaur [09/1051(0020)/2018-EMR-1]) are acknowledged for funding.

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Authors and Affiliations

  1. Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151001, India

    Prabhsimran Kaur, Sandeep Singh, Bidwan Sekhar Behera & Anjana Munshi

  2. Max Endocrinology, Diabetes and Obesity Care Centre, Max Superspeciality Hospital, Bathinda, 151001, India

    Sushil Kotru

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Key points

1. T2DM is a devastating disease.

2. miRNAs have emerged as significant biomarkers.

3. miRNAs have been implicated in the pathogenesis of T2DM.

4. miRNAs play a significant role in insulin secretion, insulin resistance and β cell dysfunction.

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Kaur, P., Kotru, S., Singh, S. et al. Role of miRNAs in the pathogenesis of T2DM, insulin secretion, insulin resistance, and β cell dysfunction: the story so far. J Physiol Biochem 76, 485–502 (2020). https://doi.org/10.1007/s13105-020-00760-2

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  • DOI: https://doi.org/10.1007/s13105-020-00760-2

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