Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

The Potential Role of Gut Microbiota in the Pathogenesis of Type 2 Diabetes Mellitus via Epigenetics and Inflammasome

Author(s): Bunty Sharma*, Aman Kumar*, Ujjawal Sharma, Deeksha Pal and Sourabh Prashar

Volume 22, Issue 14, 2022

Published on: 05 August, 2022

Page: [1331 - 1343] Pages: 13

DOI: 10.2174/1871530322666220331152809

Price: $65

Abstract

The gut microbiota that comprises over 100 trillion microorganisms with a weight of about 1-2 kg is regarded as one of the most crucial players in the regulation of the metabolic health of host organisms. In recent years, the incidence of type 2 diabetes mellitus (T2DM), characterized by high levels of sugar in the blood, has been exponentially increasing due to obesity and other lifestyle risk factors. It was shown that dysbiosis, change in the overall composition, and diversity of gut microflora can result in T2DM. Conversely, the microbial composition can also influence the epigenetics of the host organism (DNA methylation as well as histone modifications), which might have a potential effect on the metabolic health of the individual. Another mechanism of gut microbiota in the development of T2DM is through the involvement of nucleotide-binding oligomerization domain, Leucine-rich Repeat, and Pyrin domain containing 3 (NLRP3) inflammasome, a part of the innate immune system. NLRP3 inflammasome produces inflammatory cytokines, promoting the secretion of microbial antigens in the intestinal epithelium. Therefore, it is important to understand the possible connecting link between gut microbiota and T2DM that might help in the modulation of gut microflora to better understand the disease. In this review, the role of gut microbiota in the pathogenesis of T2DM will be discussed.

Keywords: Microbiota, diabetes mellitus, epigenetics, inflammasome, dysbiosis, gut.

Next »
Graphical Abstract

[1]
Kao, K.T.; Sabin, M.A. Type 2 diabetes mellitus in children and adolescents. Aust. Fam. Physician, 2016, 45(6), 401-406.
[PMID: 27622231]
[2]
International Diabetes Federation. Available from: https://www.idf.org/ (Accessed May 30, 2021).
[3]
Weisman, A.; Fazli, G.S.; Johns, A.; Booth, G.L. Evolving trends in the epidemiology, risk factors, and prevention of type 2 diabetes: A review. Can. J. Cardiol., 2018, 34(5), 552-564.
[http://dx.doi.org/10.1016/j.cjca.2018.03.002] [PMID: 29731019]
[4]
Dunachie, S.; Chamnan, P. The double burden of diabetes and global infection in low and middle-income countries. Trans. R. Soc. Trop. Med. Hyg., 2019, 113(2), 56-64.
[http://dx.doi.org/10.1093/trstmh/try124] [PMID: 30517697]
[5]
Jung, U.J.; Choi, M.S. Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int. J. Mol. Sci., 2014, 15(4), 6184-6223.
[http://dx.doi.org/10.3390/ijms15046184] [PMID: 24733068]
[6]
Kirkman, M.S.; Briscoe, V.J.; Clark, N.; Florez, H.; Haas, L.B.; Halter, J.B.; Huang, E.S.; Korytkowski, M.T.; Munshi, M.N.; Odegard, P.S.; Pratley, R.E.; Swift, C.S. Diabetes in older adults. Diabetes Care, 2012, 35(12), 2650-2664.
[http://dx.doi.org/10.2337/dc12-1801] [PMID: 23100048]
[7]
Guilherme, A.; Virbasius, J.V.; Puri, V.; Czech, M.P. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat. Rev. Mol. Cell Biol., 2008, 9(5), 367-377.
[http://dx.doi.org/10.1038/nrm2391] [PMID: 18401346]
[8]
Ismail, L.; Materwala, H.; Al Kaabi, J. Association of risk factors with type 2 diabetes: A systematic review. Comput. Struct. Biotechnol. J., 2021, 19, 1759-1785.
[http://dx.doi.org/10.1016/j.csbj.2021.03.003] [PMID: 33897980]
[9]
American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2021. Diabetes Care, 2021, 44(Suppl. 1), S15-S33.
[http://dx.doi.org/10.2337/dc21-S002] [PMID: 33298413]
[10]
Urakami, T. Maturity-onset diabetes of the young (MODY): Current perspectives on diagnosis and treatment. Diabetes Metab. Syndr. Obes., 2019, 12, 1047-1056.
[http://dx.doi.org/10.2147/DMSO.S179793] [PMID: 31360071]
[11]
Rong, Y.; Bao, W.; Shan, Z.; Liu, J.; Yu, X.; Xia, S.; Gao, H.; Wang, X.; Yao, P.; Hu, F.B.; Liu, L. Increased microRNA-146a levels in plasma of patients with newly diagnosed type 2 diabetes mellitus. PLoS One, 2013, 8(9), e73272.
[http://dx.doi.org/10.1371/journal.pone.0073272] [PMID: 24023848]
[12]
Willeit, P.; Skroblin, P.; Moschen, A.R.; Yin, X.; Kaudewitz, D.; Zampetaki, A.; Barwari, T.; Whitehead, M.; Ramírez, C.M.; Goedeke, L.; Rotllan, N.; Bonora, E.; Hughes, A.D.; Santer, P.; Fernández-Hernando, C.; Tilg, H.; Willeit, J.; Kiechl, S.; Mayr, M. Circulating microRNA-122 is associated with the risk of new-onset metabolic syndrome and type 2 diabetes. Diabetes, 2017, 66(2), 347-357.
[http://dx.doi.org/10.2337/db16-0731] [PMID: 27899485]
[13]
Vangipurapu, J.; Fernandes Silva, L.; Kuulasmaa, T.; Smith, U.; Laakso, M. Microbiota-related metabolites and the risk of type 2 diabetes. Diabetes Care, 2020, 43(6), 1319-1325.
[http://dx.doi.org/10.2337/dc19-2533] [PMID: 32295805]
[14]
Zaccardi, F.; Khunti, K.; Marx, N.; Davies, M.J. First-line treatment for type 2 diabetes: Is it too early to abandon metformin? Lancet, 2020, 396(10264), 1705-1707.
[http://dx.doi.org/10.1016/S0140-6736(20)32523-X] [PMID: 33248483]
[15]
LiverTox. Clinical and research information on drug-induced liver injury; National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda, MD, 2012.
[16]
Hinnen, D. Glucagon-like peptide 1 receptor agonists for type 2 diabetes. Diabetes Spectr., 2017, 30(3), 202-210.
[http://dx.doi.org/10.2337/ds16-0026] [PMID: 28848315]
[17]
Scheen, A.J. Cardiovascular effects of new oral glucose-lowering agents: DPP-4 and SGLT-2 inhibitors. Circ. Res., 2018, 122(10), 1439-1459.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311588] [PMID: 29748368]
[18]
Reginato, M.J.; Lazar, M.A. Mechanisms by which thiazolidinediones enhance insulin action. Trends Endocrinol. Metab., 1999, 10(1), 9-13.
[http://dx.doi.org/10.1016/S1043-2760(98)00110-6] [PMID: 10322388]
[19]
Ding, S.; Xu, S.; Ma, Y.; Liu, G.; Jang, H.; Fang, J. Modulatory mechanisms of the nlrp3 inflammasomes in diabetes. Biomolecules, 2019, 9(12), 850.
[http://dx.doi.org/10.3390/biom9120850] [PMID: 31835423]
[20]
Grice, E.A.; Segre, J.A. The skin microbiome. Nat. Rev. Microbiol., 2011, 9(4), 244-253.
[http://dx.doi.org/10.1038/nrmicro2537] [PMID: 21407241]
[21]
Yilmaz, P.; Parfrey, L.W.; Yarza, P.; Gerken, J.; Pruesse, E.; Quast, C.; Schweer, T.; Peplies, J.; Ludwig, W.; Glöckner, F.O. The SILVA and “all-species living tree project (LTP)” taxonomic frameworks. Nucleic Acids Res., 2014, 42(Database issue), D643-D648.
[http://dx.doi.org/10.1093/nar/gkt1209] [PMID: 24293649]
[22]
Ding, T.; Schloss, P.D. Dynamics and associations of microbial community types across the human body. Nature, 2014, 509(7500), 357-360.
[http://dx.doi.org/10.1038/nature13178] [PMID: 24739969]
[23]
Hoeppli, R.E.; Wu, D.; Cook, L.; Levings, M.K. The environment of regulatory T cell biology: Cytokines, metabolites, and the microbiome. Front. Immunol., 2015, 6, 61.
[http://dx.doi.org/10.3389/fimmu.2015.00061] [PMID: 25741338]
[24]
Wen, L.; Duffy, A. Factors influencing the gut microbiota, inflammation, and type 2 diabetes. J. Nutr., 2017, 147(7), 1468S-1475S.
[http://dx.doi.org/10.3945/jn.116.240754] [PMID: 28615382]
[25]
Sokol, H.; Pigneur, B.; Watterlot, L.; Lakhdari, O.; Bermúdez-Humarán, L.G.; Gratadoux, J.J.; Blugeon, S.; Bridonneau, C.; Furet, J.P.; Corthier, G.; Grangette, C.; Vasquez, N.; Pochart, P.; Trugnan, G.; Thomas, G.; Blottière, H.M.; Doré, J.; Marteau, P.; Seksik, P.; Langella, P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl. Acad. Sci. USA, 2008, 105(43), 16731-16736.
[http://dx.doi.org/10.1073/pnas.0804812105] [PMID: 18936492]
[26]
Morgan, X.C.; Huttenhower, C. Chapter 12: Human microbiome analysis. PLOS Comput. Biol., 2012, 8(12), e1002808.
[http://dx.doi.org/10.1371/journal.pcbi.1002808] [PMID: 23300406]
[27]
Pascal, M.; Perez-Gordo, M.; Caballero, T.; Escribese, M.M.; Lopez Longo, M.N.; Luengo, O.; Manso, L.; Matheu, V.; Seoane, E.; Zamorano, M.; Labrador, M.; Mayorga, C. Microbiome and allergic diseases. Front. Immunol., 2018, 9, 1584.
[http://dx.doi.org/10.3389/fimmu.2018.01584] [PMID: 30065721]
[28]
Gurung, M.; Li, Z.; You, H.; Rodrigues, R.; Jump, D.B.; Morgun, A.; Shulzhenko, N. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine, 2020, 51, 102590.
[http://dx.doi.org/10.1016/j.ebiom.2019.11.051] [PMID: 31901868]
[29]
Yamaguchi, Y.; Adachi, K.; Sugiyama, T.; Shimozato, A.; Ebi, M.; Ogasawara, N.; Funaki, Y.; Goto, C.; Sasaki, M.; Kasugai, K. Association of intestinal microbiota with metabolic markers and dietary habits in patients with type 2 diabetes. Digestion, 2016, 94(2), 66-72.
[http://dx.doi.org/10.1159/000447690] [PMID: 27504897]
[30]
Burcelin, R. Gut microbiota and immune crosstalk in metabolic disease. Mol. Metab., 2016, 5(9), 771-781.
[http://dx.doi.org/10.1016/j.molmet.2016.05.016] [PMID: 27617200]
[31]
Ferrucci, L.; Fabbri, E. Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty. Nat. Rev. Cardiol., 2018, 15(9), 505-522.
[http://dx.doi.org/10.1038/s41569-018-0064-2] [PMID: 30065258]
[32]
Karlsson, F.H.; Tremaroli, V.; Nookaew, I.; Bergström, G.; Behre, C.J.; Fagerberg, B.; Nielsen, J.; Bäckhed, F. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature, 2013, 498(7452), 99-103.
[http://dx.doi.org/10.1038/nature12198] [PMID: 23719380]
[33]
Larsen, N.; Vogensen, F.K.; van den Berg, F.W.; Nielsen, D.S.; Andreasen, A.S.; Pedersen, B.K.; Al-Soud, W.A.; Sørensen, S.J.; Hansen, L.H.; Jakobsen, M. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One, 2010, 5(2), e9085.
[http://dx.doi.org/10.1371/journal.pone.0009085] [PMID: 20140211]
[34]
Kumar, A.; Kumari, N.; Nallabelli, N.; Prasad, R. Pathogenic and therapeutic role of H3K4 family of methylases and demethylases in cancers. Indian J. Clin. Biochem., 2019, 34(2), 123-132.
[http://dx.doi.org/10.1007/s12291-019-00828-x] [PMID: 31092985]
[35]
Muka, T.; Nano, J.; Voortman, T.; Braun, K.V.E.; Ligthart, S.; Stranges, S.; Bramer, W.M.; Troup, J.; Chowdhury, R.; Dehghan, A.; Franco, O.H. The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes: A systematic review. Nutr. Metab. Cardiovasc. Dis., 2016, 26(7), 553-566.
[http://dx.doi.org/10.1016/j.numecd.2016.04.002] [PMID: 27146363]
[36]
Andreeva-Gateva, P.A.; Mihaleva, I.D.; Dimova, I.I. Type 2 diabetes mellitus and cardiovascular risk; what the pharmacotherapy can change through the epigenetics. Postgrad. Med., 2020, 132(2), 109-125.
[http://dx.doi.org/10.1080/00325481.2019.1681215] [PMID: 31615302]
[37]
Bianco-Miotto, T.; Craig, J.M.; Gasser, Y.P.; van Dijk, S.J.; Ozanne, S.E. Epigenetics and DOHaD: From basics to birth and beyond. J. Dev. Orig. Health Dis., 2017, 8(5), 513-519.
[http://dx.doi.org/10.1017/S2040174417000733] [PMID: 28889823]
[38]
Nilsson, E.; Jansson, P.A.; Perfilyev, A.; Volkov, P.; Pedersen, M.; Svensson, M.K.; Poulsen, P.; Ribel-Madsen, R.; Pedersen, N.L.; Almgren, P.; Fadista, J.; Rönn, T.; Klarlund Pedersen, B.; Scheele, C.; Vaag, A.; Ling, C. Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes, 2014, 63(9), 2962-2976.
[http://dx.doi.org/10.2337/db13-1459] [PMID: 24812430]
[39]
Gu, T.; Gu, H.F.; Hilding, A.; Östenson, C-G.; Brismar, K. DNA Methylation analysis of the insulin-like growth factor-1 (IGF1) gene in Swedish men with normal glucose tolerance and type 2 diabetes. J. Diabetes Metab., 2014, 05, 1-6.
[40]
Yang, B.T.; Dayeh, T.A.; Kirkpatrick, C.L.; Taneera, J.; Kumar, R.; Groop, L.; Wollheim, C.B.; Nitert, M.D.; Ling, C. Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets. Diabetologia, 2011, 54(2), 360-367.
[http://dx.doi.org/10.1007/s00125-010-1967-6] [PMID: 21104225]
[41]
Zhao, Z.; Shilatifard, A. Epigenetic modifications of histones in cancer. Genome Biol., 2019, 20(1), 245.
[http://dx.doi.org/10.1186/s13059-019-1870-5] [PMID: 31747960]
[42]
Väremo, L.; Henriksen, T.I.; Scheele, C.; Broholm, C.; Pedersen, M.; Uhlén, M.; Pedersen, B.K.; Nielsen, J. Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes. Genome Med., 2017, 9(1), 47.
[http://dx.doi.org/10.1186/s13073-017-0432-2] [PMID: 28545587]
[43]
Prattichizzo, F.; De Nigris, V.; Spiga, R.; Mancuso, E.; La Sala, L.; Antonicelli, R.; Testa, R.; Procopio, A.D.; Olivieri, F.; Ceriello, A. Inflammageing and metaflammation: The yin and yang of type 2 diabetes. Ageing Res. Rev., 2018, 41, 1-17.
[http://dx.doi.org/10.1016/j.arr.2017.10.003] [PMID: 29081381]
[44]
Miao, F.; Wu, X.; Zhang, L.; Yuan, Y.C.; Riggs, A.D.; Natarajan, R. Genome-wide analysis of histone lysine methylation variations caused by diabetic conditions in human monocytes. J. Biol. Chem., 2007, 282(18), 13854-13863.
[http://dx.doi.org/10.1074/jbc.M609446200] [PMID: 17339327]
[45]
Sharma, M.; Li, Y.; Stoll, M.L.; Tollefsbol, T.O. The epigenetic connection between the gut microbiome in obesity and diabetes. Front. Genet., 2020, 10, 1329.
[http://dx.doi.org/10.3389/fgene.2019.01329] [PMID: 32010189]
[46]
Sinclair, K.D.; Lea, R.G.; Rees, W.D.; Young, L.E. The developmental origins of health and disease: Current theories and epigenetic mechanisms. Soc. Reprod. Fertil. Suppl., 2007, 64(1), 425-443.
[http://dx.doi.org/10.5661/RDR-VI-425] [PMID: 17491163]
[47]
Anderson, J.W.; Baird, P.; Davis, R.H., Jr; Ferreri, S.; Knudtson, M.; Koraym, A.; Waters, V.; Williams, C.L. Health benefits of dietary fiber. Nutr. Rev., 2009, 67(4), 188-205.
[http://dx.doi.org/10.1111/j.1753-4887.2009.00189.x] [PMID: 19335713]
[48]
Kumar, H.; Lund, R.; Laiho, A.; Lundelin, K.; Ley, R.E.; Isolauri, E.; Salminen, S. Gut microbiota as an epigenetic regulator: Pilot study based on whole-genome methylation analysis. MBio, 2014, 5(6), e02113-e02114.
[http://dx.doi.org/10.1128/mBio.02113-14] [PMID: 25516615]
[49]
Cortese, R.; Lu, L.; Yu, Y.; Ruden, D.; Claud, E.C. Epigenome-Microbiome crosstalk: A potential new paradigm influencing neonatal susceptibility to disease. Epigenetics, 2016, 11(3), 205-215.
[http://dx.doi.org/10.1080/15592294.2016.1155011] [PMID: 26909656]
[50]
Yu, D.H.; Gadkari, M.; Zhou, Q.; Yu, S.; Gao, N.; Guan, Y.; Schady, D.; Roshan, T.N.; Chen, M.H.; Laritsky, E.; Ge, Z.; Wang, H.; Chen, R.; Westwater, C.; Bry, L.; Waterland, R.A.; Moriarty, C.; Hwang, C.; Swennes, A.G.; Moore, S.R.; Shen, L. Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome. Genome Biol., 2015, 16(1), 211.
[http://dx.doi.org/10.1186/s13059-015-0763-5] [PMID: 26420038]
[51]
Vahamiko, S.; Laiho, A.; Lund, R.; Isolauri, E.; Salminen, S.; Laitinen, K. The impact of probiotic supplementation during pregnancy on DNA methylation of obesity-related genes in mothers and their children. Eur. J. Nutr., 2018, 58(1), 367-377.
[52]
Zhong, T.; Men, Y.; Lu, L.; Geng, T.; Zhou, J.; Mitsuhashi, A.; Shozu, M.; Maihle, N.J.; Carmichael, G.G.; Taylor, H.S.; Huang, Y. Metformin alters DNA methylation genome-wide via the H19/SAHH axis. Oncogene, 2017, 36(17), 2345-2354.
[http://dx.doi.org/10.1038/onc.2016.391] [PMID: 27775072]
[53]
Farrelly, L.A.; Thompson, R.E.; Zhao, S.; Lepack, A.E.; Lyu, Y.; Bhanu, N.V.; Zhang, B.; Loh, Y.E.; Ramakrishnan, A.; Vadodaria, K.C.; Heard, K.J.; Erikson, G.; Nakadai, T.; Bastle, R.M.; Lukasak, B.J.; Zebroski, H., III; Alenina, N.; Bader, M.; Berton, O.; Roeder, R.G.; Molina, H.; Gage, F.H.; Shen, L.; Garcia, B.A.; Li, H.; Muir, T.W.; Maze, I. Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3. Nature, 2019, 567(7749), 535-539.
[http://dx.doi.org/10.1038/s41586-019-1024-7] [PMID: 30867594]
[54]
Mikula, M.; Majewska, A.; Ledwon, J.K.; Dzwonek, A.; Ostrowski, J. Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver. Int. J. Mol. Med., 2014, 34(6), 1647-1654.
[http://dx.doi.org/10.3892/ijmm.2014.1958] [PMID: 25319795]
[55]
Wheatley, K.E.; Nogueira, L.M.; Perkins, S.N.; Hursting, S.D. Differential effects of calorie restriction and exercise on the adipose transcriptome in diet-induced obese mice. J. Obes., 2011, 2011, 265417.
[http://dx.doi.org/10.1155/2011/265417] [PMID: 21603264]
[56]
Funato, H.; Oda, S.; Yokofujita, J.; Igarashi, H.; Kuroda, M. Fasting and high-fat diet alter histone deacetylase expression in the medial hypothalamus. PLoS One, 2011, 6(4), e18950.
[http://dx.doi.org/10.1371/journal.pone.0018950] [PMID: 21526203]
[57]
Thorburn, A.N.; Macia, L.; Mackay, C.R. Diet, metabolites, and “western-lifestyle” inflammatory diseases. Immunity, 2014, 40(6), 833-842.
[http://dx.doi.org/10.1016/j.immuni.2014.05.014] [PMID: 24950203]
[58]
Sasaki, M.; Ogasawara, N.; Funaki, Y.; Mizuno, M.; Iida, A.; Goto, C.; Koikeda, S.; Kasugai, K.; Joh, T. Transglucosidase improves the gut microbiota profile of type 2 diabetes mellitus patients: A randomized double-blind, placebo-controlled study. BMC Gastroenterol., 2013, 13(1), 81.
[http://dx.doi.org/10.1186/1471-230X-13-81] [PMID: 23657005]
[59]
Zhang, X.; Shen, D.; Fang, Z.; Jie, Z.; Qiu, X.; Zhang, C.; Chen, Y.; Ji, L. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One, 2013, 8(8), e71108.
[http://dx.doi.org/10.1371/journal.pone.0071108] [PMID: 24013136]
[60]
Cousens, L.S.; Gallwitz, D.; Alberts, B.M. Different accessibilities in chromatin to histone acetylase. J. Biol. Chem., 1979, 254(5), 1716-1723.
[http://dx.doi.org/10.1016/S0021-9258(17)37831-6] [PMID: 762168]
[61]
Stols-Gonçalves, D.; Tristão, L.S.; Henneman, P.; Nieuwdorp, M. Epigenetic markers and microbiota/metabolite-induced epigenetic modifications in the pathogenesis of obesity, metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease. Curr. Diab. Rep., 2019, 19(6), 31.
[http://dx.doi.org/10.1007/s11892-019-1151-4] [PMID: 31044315]
[62]
Sathishkumar, C.; Prabu, P.; Balakumar, M.; Lenin, R.; Prabhu, D.; Anjana, R.M.; Mohan, V.; Balasubramanyam, M. Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes. Clin. Epigenetics, 2016, 8(1), 125.
[http://dx.doi.org/10.1186/s13148-016-0293-3] [PMID: 27904654]
[63]
Dirice, E.; Ng, R.W.S.; Martinez, R.; Hu, J.; Wagner, F.F.; Holson, E.B.; Wagner, B.K.; Kulkarni, R.N. Isoform-selective inhibitor of histone deacetylase 3 (HDAC3) limits pancreatic islet infiltration and protects female nonobese diabetic mice from diabetes. J. Biol. Chem., 2017, 292(43), 17598-17608.
[http://dx.doi.org/10.1074/jbc.M117.804328] [PMID: 28860191]
[64]
Zhao, W.C.; Zhang, B.; Liao, M.J.; Zhang, W.X.; He, W.Y.; Wang, H.B.; Yang, C.X. Curcumin ameliorated diabetic neuropathy partially by inhibition of NADPH oxidase mediating oxidative stress in the spinal cord. Neurosci. Lett., 2014, 560, 81-85.
[http://dx.doi.org/10.1016/j.neulet.2013.12.019] [PMID: 24370596]
[65]
Smith, P.M.; Howitt, M.R.; Panikov, N.; Michaud, M.; Gallini, C.A.; Bohlooly-Y, M.; Glickman, J.N.; Garrett, W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 2013, 341(6145), 569-573.
[http://dx.doi.org/10.1126/science.1241165] [PMID: 23828891]
[66]
Sheikh, V.; Zamani, A.; Mahabadi-Ashtiyani, E.; Tarokhian, H.; Borzouei, S.; Alahgholi-Hajibehzad, M. Decreased regulatory function of CD4+CD25+CD45RA+ T cells and impaired IL-2 signalling pathway in patients with type 2 diabetes mellitus. Scand. J. Immunol., 2018, 88(4), e12711.
[http://dx.doi.org/10.1111/sji.12711] [PMID: 30270447]
[67]
Khan, S.; Jena, G.B. Protective role of sodium butyrate, a HDAC inhibitor on beta-cell proliferation, function and glucose homeostasis through modulation of p38/ERK MAPK and apoptotic pathways: Study in juvenile diabetic rat. Chem. Biol. Interact., 2014, 213, 1-12.
[http://dx.doi.org/10.1016/j.cbi.2014.02.001] [PMID: 24530320]
[68]
Bhat, M.I.; Kapila, R. Dietary metabolites derived from gut microbiota: Critical modulators of epigenetic changes in mammals. Nutr. Rev., 2017, 75(5), 374-389.
[http://dx.doi.org/10.1093/nutrit/nux001] [PMID: 28444216]
[69]
Soliman, M.L.; Smith, M.D.; Houdek, H.M.; Rosenberger, T.A. Acetate supplementation modulates brain histone acetylation and decreases interleukin-1β expression in a rat model of neuroinflammation. J. Neuroinflammation, 2012, 9(1), 51.
[http://dx.doi.org/10.1186/1742-2094-9-51] [PMID: 22413888]
[70]
Kasubuchi, M.; Hasegawa, S.; Hiramatsu, T.; Ichimura, A.; Kimura, I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients, 2015, 7(4), 2839-2849.
[http://dx.doi.org/10.3390/nu7042839] [PMID: 25875123]
[71]
Mariat, D.; Firmesse, O.; Levenez, F. Guimarăes, V.; Sokol, H.; Doré, J.; Corthier, G.; Furet, J.P. The firmicutes/bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol., 2009, 9(1), 123.
[http://dx.doi.org/10.1186/1471-2180-9-123] [PMID: 19508720]
[72]
Picca, A.; Fanelli, F.; Calvani, R.; Mulè, G.; Pesce, V.; Sisto, A.; Pantanelli, C.; Bernabei, R.; Landi, F.; Marzetti, E. Gut dysbiosis and muscle aging: Searching for novel targets against sarcopenia. Mediators Inflamm., 2018, 2018, 7026198.
[http://dx.doi.org/10.1155/2018/7026198] [PMID: 29686533]
[73]
Bassols, J.; Ortega, F.J.; Moreno-Navarrete, J.M.; Peral, B.; Ricart, W.; Fernández-Real, J.M. Study of the proinflammatory role of human differentiated omental adipocytes. J. Cell. Biochem., 2009, 107(6), 1107-1117.
[http://dx.doi.org/10.1002/jcb.22208] [PMID: 19492335]
[74]
Sharma, D.; Kanneganti, T.D. The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation. J. Cell Biol., 2016, 213(6), 617-629.
[http://dx.doi.org/10.1083/jcb.201602089] [PMID: 27325789]
[75]
Kelley, N.; Jeltema, D.; Duan, Y.; He, Y. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int. J. Mol. Sci., 2019, 20(13), 3328.
[http://dx.doi.org/10.3390/ijms20133328] [PMID: 31284572]
[76]
Netea, M.G.; Nold-Petry, C.A.; Nold, M.F.; Joosten, L.A.; Opitz, B.; van der Meer, J.H.; van de Veerdonk, F.L.; Ferwerda, G.; Heinhuis, B.; Devesa, I.; Funk, C.J.; Mason, R.J.; Kullberg, B.J.; Rubartelli, A.; van der Meer, J.W.; Dinarello, C.A. Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood, 2009, 113(10), 2324-2335.
[http://dx.doi.org/10.1182/blood-2008-03-146720] [PMID: 19104081]
[77]
Han, J.H.; Shin, H.; Rho, J.G.; Kim, J.E.; Son, D.H.; Yoon, J.; Lee, Y.J.; Park, J.H.; Song, B.J.; Choi, C.S.; Yoon, S.G.; Kim, I.Y.; Lee, E.K.; Seong, J.K.; Kim, K.W.; Kim, W. Peripheral cannabinoid 1 receptor blockade mitigates adipose tissue inflammation via NLRP3 inflammasome in mouse models of obesity. Diabetes Obes. Metab., 2018, 20(9), 2179-2189.
[http://dx.doi.org/10.1111/dom.13350] [PMID: 29740969]
[78]
Wu, D.; Yan, Z.B.; Cheng, Y.G.; Zhong, M.W.; Liu, S.Z.; Zhang, G.Y.; Hu, S.Y. Deactivation of the NLRP3 inflammasome in infiltrating macrophages by duodenal-jejunal bypass surgery mediates improvement of beta cell function in type 2 diabetes. Metabolism, 2018, 81, 1-12.
[http://dx.doi.org/10.1016/j.metabol.2017.10.015] [PMID: 29129820]
[79]
Esser, N.; Legrand-Poels, S.; Piette, J.; Scheen, A.J.; Paquot, N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res. Clin. Pract., 2014, 105(2), 141-150.
[http://dx.doi.org/10.1016/j.diabres.2014.04.006] [PMID: 24798950]
[80]
Youm, Y.H.; Grant, R.W.; McCabe, L.R.; Albarado, D.C.; Nguyen, K.Y.; Ravussin, A.; Pistell, P.; Newman, S.; Carter, R.; Laque, A.; Münzberg, H.; Rosen, C.J.; Ingram, D.K.; Salbaum, J.M.; Dixit, V.D. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metab., 2013, 18(4), 519-532.
[http://dx.doi.org/10.1016/j.cmet.2013.09.010] [PMID: 24093676]
[81]
Cataño Cañizales, Y.G.; Uresti Rivera, E.E.; García Jacobo, R.E.; Portales Perez, D.P.; Yadira, B.; Rodriguez Rivera, J.G.; Amaro, R.G.; Enciso Moreno, J.A.; García Hernández, M.H. Increased levels of AIM2 and circulating mitochondrial DNA in type 2 diabetes. Iran. J. Immunol., 2018, 15(2), 142-155.
[PMID: 29947343]
[82]
Sharma, B.R.; Karki, R.; Kanneganti, T.D. Role of AIM2 inflammasome in inflammatory diseases, cancer and infection. Eur. J. Immunol., 2019, 49(11), 1998-2011.
[http://dx.doi.org/10.1002/eji.201848070] [PMID: 31372985]
[83]
Brunkwall, L.; Orho-Melander, M. The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: From current human evidence to future possibilities. Diabetologia, 2017, 60(6), 943-951.
[http://dx.doi.org/10.1007/s00125-017-4278-3] [PMID: 28434033]
[84]
Kim, Y.A.; Keogh, J.B.; Clifton, P.M. Probiotics, prebiotics, synbiotics and insulin sensitivity. Nutr. Res. Rev., 2018, 31(1), 35-51.
[http://dx.doi.org/10.1017/S095442241700018X] [PMID: 29037268]
[85]
Sharma, P.; Bhardwaj, P.; Singh, R. Administration of lactobacillus casei and Bifidobacterium bifidum ameliorated hyperglycemia, dyslipidemia, and oxidative stress in diabetic rats. Int. J. Prev. Med., 2016, 7(1), 102.
[http://dx.doi.org/10.4103/2008-7802.188870] [PMID: 27625767]
[86]
Bock, P.M.; Telo, G.H.; Ramalho, R.; Sbaraini, M.; Leivas, G.; Martins, A.F.; Schaan, B.D. The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: A systematic review and meta-analysis. Diabetologia, 2021, 64(1), 26-41.
[http://dx.doi.org/10.1007/s00125-020-05295-1] [PMID: 33047170]
[87]
Vrieze, A.; Van Nood, E.; Holleman, F.; Salojärvi, J.; Kootte, R.S.; Bartelsman, J.F.; Dallinga-Thie, G.M.; Ackermans, M.T.; Serlie, M.J.; Oozeer, R.; Derrien, M.; Druesne, A.; Van Hylckama Vlieg, J.E.; Bloks, V.W.; Groen, A.K.; Heilig, H.G.; Zoetendal, E.G.; Stroes, E.S.; de Vos, W.M.; Hoekstra, J.B.; Nieuwdorp, M. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology, 2012, 143(4), 913-6.e7.
[http://dx.doi.org/10.1053/j.gastro.2012.06.031] [PMID: 22728514]
[88]
Zhang, P.P.; Li, L.L.; Han, X.; Li, Q.W.; Zhang, X.H.; Liu, J.J.; Wang, Y. Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice. Acta Pharmacol. Sin., 2020, 41(5), 678-685.
[http://dx.doi.org/10.1038/s41401-019-0330-9] [PMID: 31937933]
[89]
Wu, H.; Esteve, E.; Tremaroli, V.; Khan, M.T.; Caesar, R.; Mannerås-Holm, L.; Ståhlman, M.; Olsson, L.M.; Serino, M.; Planas-Fèlix, M.; Xifra, G.; Mercader, J.M.; Torrents, D.; Burcelin, R.; Ricart, W.; Perkins, R.; Fernàndez-Real, J.M.; Bäckhed, F. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med., 2017, 23(7), 850-858.
[http://dx.doi.org/10.1038/nm.4345] [PMID: 28530702]
[90]
Arora, T.; Bäckhed, F. The gut microbiota and metabolic disease: Current understanding and future perspectives. J. Intern. Med., 2016, 280(4), 339-349.
[http://dx.doi.org/10.1111/joim.12508] [PMID: 27071815]
[91]
Hara, S.; Hamada, J.; Kobayashi, C.; Kondo, Y.; Imura, N. Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: Suppression of HIF-mediated gene expression by HIF-3alpha. Biochem. Biophys. Res. Commun., 2001, 287(4), 808-813.
[http://dx.doi.org/10.1006/bbrc.2001.5659] [PMID: 11573933]
[92]
Maynard, M.A.; Evans, A.J.; Hosomi, T.; Hara, S.; Jewett, M.A.; Ohh, M. Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma. FASEB J., 2005, 19(11), 1396-1406.
[http://dx.doi.org/10.1096/fj.05-3788com] [PMID: 16126907]
[93]
Tanaka, T.; Wiesener, M.; Bernhardt, W.; Eckardt, K.U.; Warnecke, C. The human HIF (hypoxia-inducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction. Biochem. J., 2009, 424(1), 143-151.
[http://dx.doi.org/10.1042/BJ20090120] [PMID: 19694616]
[94]
Yokoyama, C.; Wang, X.; Briggs, M.R.; Admon, A.; Wu, J.; Hua, X.; Goldstein, J.L.; Brown, M.S. SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell, 1993, 75(1), 187-197.
[http://dx.doi.org/10.1016/S0092-8674(05)80095-9] [PMID: 8402897]
[95]
Heredia, V.V.; Carlson, T.J.; Garcia, E.; Sun, S. Biochemical basis of glucokinase activation and the regulation by glucokinase regulatory protein in naturally occurring mutations. J. Biol. Chem., 2006, 281(52), 40201-40207.
[http://dx.doi.org/10.1074/jbc.M607987200] [PMID: 17082186]
[96]
Takeda, J.; Gidh-Jain, M.; Xu, L.Z.; Froguel, P.; Velho, G.; Vaxillaire, M.; Cohen, D.; Shimada, F.; Makino, H.; Nishi, S. Structure/function studies of human beta-cell glucokinase. Enzymatic properties of a sequence polymorphism, mutations associated with diabetes, and other site-directed mutants. J. Biol. Chem., 1993, 268(20), 15200-15204.
[http://dx.doi.org/10.1016/S0021-9258(18)82456-5] [PMID: 8325892]
[97]
Prip-Buus, C.; Thuillier, L.; Abadi, N.; Prasad, C.; Dilling, L.; Klasing, J.; Demaugre, F.; Greenberg, C.R.; Haworth, J.C.; Droin, V.; Kadhom, N.; Gobin, S.; Kamoun, P.; Girard, J.; Bonnefont, J.P. Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase 1A mutation in the Hutterite community. Mol. Genet. Metab., 2001, 73(1), 46-54.
[http://dx.doi.org/10.1006/mgme.2001.3176] [PMID: 11350182]
[98]
Gu, H.M.; Wang, F.Q.; Zhang, D.W. Caveolin-1 interacts with ATP binding cassette transporter G1 (ABCG1) and regulates ABCG1-mediated cholesterol efflux. Biochim. Biophys. Acta, 2014, 1841(6), 847-858.
[http://dx.doi.org/10.1016/j.bbalip.2014.02.002] [PMID: 24576892]
[99]
Fritzius, T.; Frey, A.D.; Schweneker, M.; Mayer, D.; Moelling, K. WD-repeat-propeller-FYVE protein, ProF, binds VAMP2 and protein kinase Czeta. FEBS J., 2007, 274(6), 1552-1566.
[http://dx.doi.org/10.1111/j.1742-4658.2007.05702.x] [PMID: 17313651]
[100]
Liyanage, N.P.; Fernando, M.R.; Lou, M.F. Regulation of the bioavailability of thioredoxin in the lens by a specific thioredoxin-binding protein (TBP-2). Exp. Eye Res., 2007, 85(2), 270-279.
[http://dx.doi.org/10.1016/j.exer.2007.05.001] [PMID: 17603038]
[101]
Jin, H.O.; Seo, S.K.; Kim, Y.S.; Woo, S.H.; Lee, K.H.; Yi, J.Y.; Lee, S.J.; Choe, T.B.; Lee, J.H.; An, S.; Hong, S.I.; Park, I.C. TXNIP potentiates Redd1-induced mTOR suppression through stabilization of Redd1. Oncogene, 2011, 30(35), 3792-3801.
[http://dx.doi.org/10.1038/onc.2011.102] [PMID: 21460850]
[102]
Roberts, S.J.; Stewart, A.J.; Sadler, P.J.; Farquharson, C. Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities. Biochem. J., 2004, 382(Pt 1), 59-65.
[http://dx.doi.org/10.1042/BJ20040511] [PMID: 15175005]
[103]
Shen, Y.; Wei, W.; Zhou, D.X. Histone acetylation enzymes coordinate metabolism and gene expression. Trends Plant Sci., 2015, 20(10), 614-621.
[http://dx.doi.org/10.1016/j.tplants.2015.07.005] [PMID: 26440431]
[104]
Cao, X.; Chen, Y.; Wu, B.; Wang, X.; Xue, H.; Yu, L.; Li, J.; Wang, Y.; Wang, W.; Xu, Q.; Mao, H.; Peng, C.; Han, G.; Chen, C.D. Histone H4K20 demethylation by Two hHR23 proteins. Cell Rep., 2020, 30(12), 4152-4164.e6.
[http://dx.doi.org/10.1016/j.celrep.2020.03.001] [PMID: 32209475]
[105]
Cao, J.; Yan, Q. Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Front. Oncol., 2012, 2, 26.
[http://dx.doi.org/10.3389/fonc.2012.00026] [PMID: 22649782]
[106]
Ting, X.; Xia, L.; Yang, J.; He, L.; Si, W.; Shang, Y.; Sun, L. USP11 acts as a histone deubiquitinase functioning in chromatin reorganization during DNA repair. Nucleic Acids Res., 2019, 47(18), 9721-9740.
[http://dx.doi.org/10.1093/nar/gkz726] [PMID: 31504778]
[107]
Wang, Y.; Dasso, M. SUMOylation and deSUMOylation at a glance. J. Cell Sci., 2009, 122(Pt 23), 4249-4252.
[http://dx.doi.org/10.1242/jcs.050542] [PMID: 19923268]
[108]
Narang, M.A.; Dumas, R.; Ayer, L.M.; Gravel, R.A. Reduced histone biotinylation in multiple carboxylase deficiency patients: A nuclear role for holocarboxylase synthetase. Hum. Mol. Genet., 2004, 13(1), 15-23.
[http://dx.doi.org/10.1093/hmg/ddh006] [PMID: 14613969]
[109]
Pestinger, V.; Wijeratne, S.S.; Rodriguez-Melendez, R.; Zempleni, J. Novel histone biotinylation marks are enriched in repeat regions and participate in repression of transcriptionally competent genes. J. Nutr. Biochem., 2011, 22(4), 328-333.
[http://dx.doi.org/10.1016/j.jnutbio.2010.02.011] [PMID: 20691578]
[110]
Witalison, E.E.; Thompson, P.R.; Hofseth, L.J. Protein arginine deiminases and associated citrullination: Physiological functions and diseases associated with dysregulation. Curr. Drug Targets, 2015, 16(7), 700-710.
[http://dx.doi.org/10.2174/1389450116666150202160954] [PMID: 25642720]
[111]
Sabari, B.R.; Zhang, D.; Allis, C.D.; Zhao, Y. Metabolic regulation of gene expression through histone acylations. Nat. Rev. Mol. Cell Biol., 2017, 18(2), 90-101.
[http://dx.doi.org/10.1038/nrm.2016.140] [PMID: 27924077]

Rights & Permissions Print Cite
Article Metrics
11
© 2025 Bentham Science Publishers | Privacy Policy