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
Mini-Review Article

Antidiabetic Drugs and their Potential Use in COVID-19: A Mechanistic Approach

Author(s): Bryan Alejandro Espinosa-Rodriguez, Aissa Michelle Nieto-Moreno, Jose Luis Gonzalez Llerena, Tania Alejandra Rico-Torres, Pilar Carranza-Rosales, Luis Fernando Mendez-Lopez and Isaias Balderas-Renteria*

Volume 23, Issue 3, 2023

Published on: 03 September, 2022

Page: [255 - 272] Pages: 18

DOI: 10.2174/1871530322666220516115604

Price: $65

Abstract

Many therapies have been developed against COVID-19 since it first appeared in December 2019. Antivirals, antimalarials, cephalosporins, colchicine, anticoagulants, and corticosteroids, among others, have been evaluated as protecting agents against antibacterial complications due to their anti-inflammatory and immunomodulatory effects against thrombosis and cell death caused by infection with SARS-CoV-2. Nevertheless, the overall balance in their application has not been found to be satisfactory. On the other hand, developing and applying several vaccines against this virus have marked an important watershed in preventive and prophylactic medicine in the new millennium. However, given the regular efficacy reported of some of them, the still scarce affordability, and the emergency of new strains for which no drug has been evaluated, the search for new pharmacological therapy alternatives still represents an essential component in the clinical management of COVID-19, and the rapid identification of drugs with potential antiviral and/or immunomodulatory properties is needed. In the present review, a potential therapeutic effect of metformin and other antidiabetic therapies for the management of COVID-19 are proposed and discussed from the viewpoint of their in vitro and in vivo immunomodulatory effects. Given that acute inflammation is an important component of COVID-19, antidiabetic therapies could be promising alternatives in its management and reducing the disease's severity. In order to understand how metformin and other antidiabetic therapies could work in the context of COVID-19, here we review the possible mechanisms of action through a detailed description of cellular and molecular events.

Keywords: COVID-19, immunity, metabolism, inflammation, metformin, AMPK.

Next »
Graphical Abstract

[1]
Ksiazek, T.G.; Erdman, D.; Goldsmith, C.S.; Zaki, S.R.; Peret, T.; Emery, S.; Tong, S.; Urbani, C.; Comer, J.A.; Lim, W.; Rollin, P.E.; Dowell, S.F.; Ling, A.E.; Humphrey, C.D.; Shieh, W.J.; Guarner, J.; Paddock, C.D.; Rota, P.; Fields, B.; DeRisi, J.; Yang, J.Y.; Cox, N.; Hughes, J.M.; LeDuc, J.W.; Bellini, W.J.; Anderson, L.J. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med., 2003, 348(20), 1953-1966.
[http://dx.doi.org/10.1056/NEJMoa030781] [PMID: 12690092]
[2]
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol., 2020, 5(4), 536-544.
[http://dx.doi.org/10.1038/s41564-020-0695-z] [PMID: 32123347]
[3]
WHO. Coronavirus disease (COVID-19). Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/coronavirus-disease-covid-19 (Accessed on Aug 16, 2021).
[4]
WHO. WHO Coronavirus (COVID-19). Available from: https://covid19.who.int/ (Accessed on Aug 16, 2021).
[5]
Meo, S.A.; Klonoff, D.C.; Akram, J. Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(8), 4539-4547.
[http://dx.doi.org/10.26355/eurrev_202004_21038] [PMID: 32373993]
[6]
Takla, M.; Jeevaratnam, K. Chloroquine, hydroxychloroquine, and COVID-19: Systematic review and narrative synthesis of efficacy and safety. Saudi Pharm. J., 2020, 28(12), 1760-1776.
[http://dx.doi.org/10.1016/j.jsps.2020.11.003] [PMID: 33204210]
[7]
Ho, T.C.; Wang, Y.H.; Chen, Y.L.; Tsai, W.C.; Lee, C.H.; Chuang, K.P.; Chen, Y.A.; Yuan, C.H.; Ho, S.Y.; Yang, M.H.; Tyan, Y.C. Chloroquine and hydroxychloroquine: Efficacy in the treatment of the COVID-19. Pathogens, 2021, 10(2), 1-9.
[http://dx.doi.org/10.3390/pathogens10020217] [PMID: 33671315]
[8]
Giacobbe, D.R.; Russo, C.; Martini, V.; Dettori, S.; Briano, F.; Mirabella, M.; Portunato, F.; Dentone, C.; Mora, S.; Giacomini, M.; Berruti, M.; Bassetti, M. Use of ceftaroline in hospitalized patients with and without COVID-19: A descriptive cross-sectional study. Antibiotics (Basel), 2021, 10(7), 1-10.
[http://dx.doi.org/10.3390/antibiotics10070763] [PMID: 34201722]
[9]
Mangkuliguna, G. Glenardi; Natalia; Pramono, L.A. Efficacy and safety of azithromycin for the treatment of COVID-19: A systematic review and meta-analysis. Tuberc. Respir. Dis. (Seoul), 2021, 84(4), 299-316.
[http://dx.doi.org/10.4046/trd.2021.0075] [PMID: 34015868]
[10]
Tardif, J.C.; Bouabdallaoui, N.; L’Allier, P.L.; Gaudet, D.; Shah, B.; Pillinger, M.H.; Lopez-Sendon, J.; da Luz, P.; Verret, L.; Audet, S.; Dupuis, J.; Denault, A.; Pelletier, M.; Tessier, P.A.; Samson, S.; Fortin, D.; Tardif, J.D.; Busseuil, D.; Goulet, E.; Lacoste, C.; Dubois, A.; Joshi, A.Y.; Waters, D.D.; Hsue, P.; Lepor, N.E.; Lesage, F.; Sainturet, N.; Roy-Clavel, E.; Bassevitch, Z.; Orfanos, A.; Stamatescu, G.; Grégoire, J.C.; Busque, L.; Lavallée, C.; Hétu, P.O.; Paquette, J.S.; Deftereos, S.G.; Levesque, S.; Cossette, M.; Nozza, A.; Chabot-Blanchet, M.; Dubé, M.P.; Guertin, M.C.; Boivin, G. Colchicine for community-treated patients with COVID-19 (COLCORONA): A phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir. Med., 2021, 9(8), 924-932.
[http://dx.doi.org/10.1016/S2213-2600(21)00222-8] [PMID: 34051877]
[11]
Osborne, V.; Davies, M.; Lane, S.; Evans, A.; Denyer, J.; Dhanda, S.; Roy, D.; Shakir, S. Lopinavir-ritonavir in the treatment of COVID-19: A dynamic systematic benefit-risk assessment. Drug Saf., 2020, 43(8), 809-821.
[http://dx.doi.org/10.1007/s40264-020-00966-9] [PMID: 32578156]
[12]
Horby, P.W.; Mafham, M.; Bell, J.L.; Linsell, L.; Staplin, N.; Emberson, J.; Palfreeman, A.; Raw, J.; Elmahi, E.; Prudon, B.; Green, C.; Carley, S.; Chadwick, D.; Davies, M.; Wise, M.P.; Baillie, J.K.; Chappell, L.C.; Faust, S.N.; Jaki, T.; Jefferey, K.; Lim, W.S.; Montgomery, A.; Rowan, K.; Juszczak, E.; Haynes, R.; Landray, M.J. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet, 2020, 396(10259), 1345-1352.
[http://dx.doi.org/10.1016/S0140-6736(20)32013-4] [PMID: 33031764]
[13]
Goldman, J.D.; Lye, D.C.B.; Hui, D.S.; Marks, K.M.; Bruno, R.; Montejano, R.; Spinner, C.D.; Galli, M.; Ahn, M-Y.; Nahass, R.G.; Chen, Y.S.; SenGupta, D.; Hyland, R.H.; Osinusi, A.O.; Cao, H.; Blair, C.; Wei, X.; Gaggar, A.; Brainard, D.M.; Towner, W.J.; Muñoz, J.; Mullane, K.M.; Marty, F.M.; Tashima, K.T.; Diaz, G.; Subramanian, A. Remdesivir for 5 or 10 days in patients with severe Covid-19. N. Engl. J. Med., 2020, 383(19), 1827-1837.
[http://dx.doi.org/10.1056/NEJMoa2015301] [PMID: 32459919]
[14]
Kaka, A.S.; MacDonald, R.; Greer, N.; Vela, K.; Duan-Porter, W.; Obley, A.; Wilt, T.J. Major update: Remdesivir for adults with COVID-19: A living systematic review and meta-analysis for the American College of Physicians Practice Points. Ann. Intern. Med., 2021, 174(5), 663-672.
[http://dx.doi.org/10.7326/M20-8148] [PMID: 33560863]
[15]
Billett, H.H.; Reyes-Gil, M.; Szymanski, J.; Ikemura, K.; Stahl, L.R.; Lo, Y.; Rahman, S.; Gonzalez-Lugo, J.D.; Kushnir, M.; Barouqa, M.; Golestaneh, L.; Bellin, E. Anticoagulation in COVID-19: Effect of enoxaparin, heparin, and apixaban on mortality. Thromb. Haemost., 2020, 120(12), 1691-1699.
[http://dx.doi.org/10.1055/s-0040-1720978] [PMID: 33186991]
[16]
Di Castelnuovo, A.; Costanzo, S.; Antinori, A.; Berselli, N.; Blandi, L.; Bonaccio, M.; Cauda, R.; Guaraldi, G.; Menicanti, L.; Mennuni, M.; Parruti, G.; Patti, G.; Santilli, F.; Signorelli, C.; Vergori, A.; Abete, P.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Al Moghazi, S.; Arboretti, R.; Astuto, M.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Carrozzi, L.; Cascio, A.; Ciccullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Colombo, C.; Crosta, F.; Danzi, G.B.; D’Ardes, D.; de Gaetano Donati, K.; Di Gennaro, F.; Di Tano, G.; D’Offizi, G.; Fantoni, M.; Fusco, F.M.; Gentile, I.; Gianfagna, F.; Grandone, E.; Graziani, E.; Grisafi, L.; Guarnieri, G.; Larizza, G.; Leone, A.; Maccagni, G.; Madaro, F.; Maitan, S.; Mancarella, S.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marongiu, S.; Marotta, C.; Marra, L.; Mastroianni, F.; Mazzitelli, M.; Mengozzi, A.; Menichetti, F.; Meschiari, M.; Milic, J.; Minutolo, F.; Molena, B.; Montineri, A.; Mussini, C.; Musso, M.; Niola, D.; Odone, A.; Olivieri, M.; Palimodde, A.; Parisi, R.; Pasi, E.; Pesavento, R.; Petri, F.; Pinchera, B.; Poletti, V.; Ravaglia, C.; Rognoni, A.; Rossato, M.; Rossi, M.; Sangiovanni, V.; Sanrocco, C.; Scorzolini, L.; Sgariglia, R.; Simeone, P.G.; Taddei, E.; Torti, C.; Vettor, R.; Vianello, A.; Vinceti, M.; Virano, A.; Vocciante, L.; De Caterina, R.; Iacoviello, L. Heparin in COVID-19 patients is associated with reduced in-hospital mortality: The multicenter Italian Corist study. Thromb. Haemost., 2021, 121(8), 1054-1065.
[http://dx.doi.org/10.1055/a-1347-6070] [PMID: 33412596]
[17]
Hasan, M.J.; Rabbani, R.; Anam, A.M.; Huq, S.M.R.; Polash, M.M.I.; Nessa, S.S.T.; Bachar, S.C. Impact of high dose of baricitinib in severe COVID-19 pneumonia: A prospective cohort study in Bangladesh. BMC Infect. Dis., 2021, 21(1), 427.
[http://dx.doi.org/10.1186/s12879-021-06119-2] [PMID: 33962573]
[18]
Kalil, A.C.; Patterson, T.F.; Mehta, A.K.; Tomashek, K.M.; Wolfe, C.R.; Ghazaryan, V.; Marconi, V.C.; Ruiz-Palacios, G.M.; Hsieh, L.; Kline, S.; Tapson, V.; Iovine, N.M.; Jain, M.K.; Sweeney, D.A.; El Sahly, H.M.; Branche, A.R.; Regalado Pineda, J.; Lye, D.C.; Sandkovsky, U.; Luetkemeyer, A.F.; Cohen, S.H.; Finberg, R.W.; Jackson, P.E.H.; Taiwo, B.; Paules, C.I.; Arguinchona, H.; Erdmann, N.; Ahuja, N.; Frank, M.; Oh, M.D.; Kim, E.S.; Tan, S.Y.; Mularski, R.A.; Nielsen, H.; Ponce, P.O.; Taylor, B.S.; Larson, L.; Rouphael, N.G.; Saklawi, Y.; Cantos, V.D.; Ko, E.R.; Engemann, J.J.; Amin, A.N.; Watanabe, M.; Billings, J.; Elie, M.C.; Davey, R.T.; Burgess, T.H.; Ferreira, J.; Green, M.; Makowski, M.; Cardoso, A.; de Bono, S.; Bonnett, T.; Proschan, M.; Deye, G.A.; Dempsey, W.; Nayak, S.U.; Dodd, L.E.; Beigel, J.H. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N. Engl. J. Med., 2021, 384(9), 795-807.
[http://dx.doi.org/10.1056/NEJMoa2031994] [PMID: 33306283]
[19]
Wang, D.; Fu, B.; Peng, Z.; Yang, D.; Han, M.; Li, M.; Yang, Y.; Yang, T.; Sun, L.; Li, W.; Shi, W.; Yao, X.; Ma, Y.; Xu, F.; Wang, X.; Chen, J.; Xia, D.; Sun, Y.; Dong, L.; Wang, J.; Zhu, X.; Zhang, M.; Zhou, Y.; Pan, A.; Hu, X.; Mei, X.; Wei, H.; Xu, X. Tocilizumab in patients with moderate or severe COVID-19: A randomized, controlled, open-label, multicenter trial. Front. Med., 2021, 15(3), 486-494.
[http://dx.doi.org/10.1007/s11684-020-0824-3] [PMID: 33687643]
[20]
Rosas, I.O.; Bräu, N.; Waters, M.; Go, R.C.; Hunter, B.D.; Bhagani, S.; Skiest, D.; Aziz, M.S.; Cooper, N.; Douglas, I.S.; Savic, S.; Youngstein, T.; Del Sorbo, L.; Cubillo Gracian, A.; De La Zerda, D.J.; Ustianowski, A.; Bao, M.; Dimonaco, S.; Graham, E.; Matharu, B.; Spotswood, H.; Tsai, L.; Malhotra, A. Tocilizumab in hospitalized patients with severe COVID-19 pneumonia. N. Engl. J. Med., 2021, 384(16), 1503-1516.
[http://dx.doi.org/10.1056/NEJMoa2028700] [PMID: 33631066]
[21]
Monemi, S.; Berber, E.; Sarsour, K.; Wang, J.; Lampl, K.; Bharucha, K.; Pethoe-Schramm, A. Incidence of gastrointestinal perforations in patients with rheumatoid arthritis treated with tocilizumab from clinical trial, postmarketing, and real-world data sources. Rheumatol. Ther., 2016, 3(2), 337-352.
[http://dx.doi.org/10.1007/s40744-016-0037-z] [PMID: 27747579]
[22]
Ikeda, S.; Misumi, T.; Izumi, S.; Sakamoto, K.; Nishimura, N.; Ro, S.; Fukunaga, K.; Okamori, S.; Tachikawa, N.; Miyata, N.; Shinkai, M.; Shinoda, M.; Miyazaki, Y.; Iijima, Y.; Izumo, T.; Inomata, M.; Okamoto, M.; Yamaguchi, T.; Iwabuchi, K.; Masuda, M.; Takoi, H.; Oyamada, Y.; Fujitani, S.; Mineshita, M.; Ishii, H.; Nakagawa, A.; Yamaguchi, N.; Hibino, M.; Tsushima, K.; Nagai, T.; Ishikawa, S.; Ishikawa, N.; Kondoh, Y.; Yamazaki, Y.; Gocho, K.; Nishizawa, T.; Tsuzuku, A.; Yagi, K.; Shindo, Y.; Takeda, Y.; Yamanaka, T.; Ogura, T. Corticosteroids for hospitalized patients with mild to critically-ill COVID-19: A multicenter, retrospective, propensity score-matched study. Sci. Rep., 2021, 11(1), 10727.
[http://dx.doi.org/10.1038/s41598-021-90246-y] [PMID: 34021229]
[23]
Horby, P.; Lim, W.S.; Emberson, J.R.; Mafham, M.; Bell, J.L.; Linsell, L.; Staplin, N.; Brightling, C.; Ustianowski, A.; Elmahi, E.; Prudon, B.; Green, C.; Felton, T.; Chadwick, D.; Rege, K.; Fegan, C.; Chappell, L.C.; Faust, S.N.; Jaki, T.; Jeffery, K.; Montgomery, A.; Rowan, K.; Juszczak, E.; Baillie, J.K.; Haynes, R.; Landray, M.J. Dexamethasone in hospitalized patients with COVID-19. N. Engl. J. Med., 2021, 384(8), 693-704.
[http://dx.doi.org/10.1056/NEJMoa2021436] [PMID: 32678530]
[24]
Moghadas, S.M.; Vilches, T.N.; Zhang, K.; Wells, C.R.; Shoukat, A.; Singer, B.H.; Meyers, L.A.; Neuzil, K.M.; Langley, J.M.; Fitzpatrick, M.C.; Galvani, A.P. The impact of vaccination on coronavirus disease 2019 (COVID-19) outbreaks in the United States. Clin. Infect. Dis., 2021, 73(12), 2257-2264.
[http://dx.doi.org/10.1093/cid/ciab079] [PMID: 33515252]
[25]
Moline, H. L.; Whitaker, M.; Deng, L.; Rhodes, J. C.; Milucky, J.; Pham, H. Effectiveness of COVID-19 vaccines in preventing hospitalization among adults aged ≥ 65 years - COVID-NET , 13 States , February - April 2021. 2021, 70(32), 1088-1093.
[http://dx.doi.org/10.15585/mmwr.mm7032e3]
[26]
Alencar, C.H.; Cavalcanti, L.P.G.; Almeida, M.M.; Barbosa, P.P.L.; Cavalcante, K.K.S.; Melo, D.N.; de Brito Alves, B.C.F.; Heukelbach, J. High effectiveness of SARS-CoV-2 vaccines in reducing COVID-19-related deaths in over 75-year-olds, Ceará State, Brazil. Trop. Med. Infect. Dis., 2021, 6(3), 129.
[http://dx.doi.org/10.3390/tropicalmed6030129] [PMID: 34287384]
[27]
Wouters, O.J.; Shadlen, K.C.; Salcher-Konrad, M.; Pollard, A.J.; Larson, H.J.; Teerawattananon, Y.; Jit, M. Challenges in ensuring global access to COVID-19 vaccines: Production, affordability, allocation, and deployment. Lancet, 2021, 397(10278), 1023-1034.
[http://dx.doi.org/10.1016/S0140-6736(21)00306-8] [PMID: 33587887]
[28]
Bian, L.; Gao, F.; Zhang, J.; He, Q.; Mao, Q.; Xu, M.; Liang, Z. Effects of SARS-CoV-2 variants on vaccine efficacy and response strategies. Expert Rev. Vaccines, 2021, 20(4), 365-373.
[http://dx.doi.org/10.1080/14760584.2021.1903879] [PMID: 33851875]
[29]
Bailey, C.J.; Day, C. Metformin: Its botanical background. Pract. Diabetes Int., 2004, 21(3), 115-117.
[http://dx.doi.org/10.1002/pdi.606]
[30]
Bergman, U.; Boman, G.; Wiholm, B.E. Epidemiology of adverse drug reactions to phenformin and metformin. BMJ, 1978, 2(6135), 464-466.
[http://dx.doi.org/10.1136/bmj.2.6135.464] [PMID: 678924]
[31]
Grygiel-Górniak, B. Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications--a review. Nutr. J., 2014, 13(1), 17.
[http://dx.doi.org/10.1186/1475-2891-13-17] [PMID: 24524207]
[32]
Zeng, F.; Huang, Y.; Guo, Y.; Yin, M.; Chen, X.; Xiao, L.; Deng, G. Association of inflammatory markers with the severity of COVID-19: A meta-analysis. Int. J. Infect. Dis., 2020, 96, 467-474.
[http://dx.doi.org/10.1016/j.ijid.2020.05.055] [PMID: 32425643]
[33]
Han, T.; Ma, S.; Sun, C.; Zhang, H.; Qu, G.; Chen, Y.; Cheng, C. The association between anti-diabetic agents and clinical outcomes of COVID-19 in patients with diabetes: A systematic review and meta-analysis. Arch. Med. Res., 2022, 53(2), 186-195.
[http://dx.doi.org/10.1016/j.arcmed.2021.08.002] [PMID: 34412904]
[34]
Yang, W.; Sun, X.; Zhang, J.; Zhang, K. The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus. Clin. Pract., 2021, 178(108977), 108977.
[http://dx.doi.org/10.1016/j.diabres.2021.108977] [PMID: 34302912]
[35]
Poly, T.N.; Islam, M.M.; Li, Y.J.; Lin, M.C.; Hsu, M.H.; Wang, Y.C. Metformin use is associated with decreased mortality in COVID-19 patients with diabetes: Evidence from retrospective studies and biological mechanism. J. Clin. Med., 2021, 10(16), 3507.
[http://dx.doi.org/10.3390/jcm10163507] [PMID: 34441802]
[36]
Salian, V.S.; Wright, J.A.; Vedell, P.T.; Nair, S.; Li, C.; Kandimalla, M.; Tang, X.; Porquera, C.E.M.; Kalari, K.R.; Kandimalla, K.K. COVID-19 transmission, current treatment, and future therapeutic strategies. Mol. Pharm., 2021, 18(3), 754-771.
[http://dx.doi.org/10.1021/acs.molpharmaceut.0c00608] [PMID: 33464914]
[37]
van Doremalen, N.; Bushmaker, T.; Morris, D.H.; Holbrook, M.G.; Gamble, A.; Williamson, B.N.; Tamin, A.; Harcourt, J.L.; Thornburg, N.J.; Gerber, S.I.; Lloyd-Smith, J.O.; de Wit, E.; Munster, V.J. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N. Engl. J. Med., 2020, 382(16), 1564-1567.
[http://dx.doi.org/10.1056/NEJMc2004973] [PMID: 32182409]
[38]
Babcock, G.J.; Esshaki, D.J.; Thomas, W.D., Jr; Ambrosino, D.M. Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor. J. Virol., 2004, 78(9), 4552-4560.
[http://dx.doi.org/10.1128/JVI.78.9.4552-4560.2004] [PMID: 15078936]
[39]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2), 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[40]
Chan, J.F.W.; Kok, K.H.; Zhu, Z.; Chu, H.; To, K.K.W.; Yuan, S.; Yuen, K.Y. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg. Microbes Infect., 2020, 9(1), 221-236.
[http://dx.doi.org/10.1080/22221751.2020.1719902] [PMID: 31987001]
[41]
Wang, Q.; Zhang, Y.; Wu, L.; Niu, S.; Song, C.; Zhang, Z.; Lu, G.; Qiao, C.; Hu, Y.; Yuen, K.Y.; Wang, Q.; Zhou, H.; Yan, J.; Qi, J. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell, 2020, 181(4), 894-904.e9.
[http://dx.doi.org/10.1016/j.cell.2020.03.045] [PMID: 32275855]
[42]
Letko, M.; Marzi, A.; Munster, V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol., 2020, 5(4), 562-569.
[http://dx.doi.org/10.1038/s41564-020-0688-y] [PMID: 32094589]
[43]
Karthika, T.; Joseph, J.; Das, V.R.A.; Nair, N.; Charulekha, P.; Roji, M.D.; Raj, V.S. SARS-CoV-2 cellular entry is independent of the ACE2 cytoplasmic domain signaling. Cells, 2021, 10(7), 1814.
[http://dx.doi.org/10.3390/cells10071814] [PMID: 34359983]
[44]
Wang, S.; Qiu, Z.; Hou, Y.; Deng, X.; Xu, W.; Zheng, T.; Wu, P.; Xie, S.; Bian, W.; Zhang, C.; Sun, Z.; Liu, K.; Shan, C.; Lin, A.; Jiang, S.; Xie, Y.; Zhou, Q.; Lu, L.; Huang, J.; Li, X. AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells. Cell Res., 2021, 31(2), 126-140.
[http://dx.doi.org/10.1038/s41422-020-00460-y] [PMID: 33420426]
[45]
Hamming, I.; Timens, W.; Bulthuis, M.L.C.; Lely, A.T.; Navis, G.; van Goor, H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol., 2004, 203(2), 631-637.
[http://dx.doi.org/10.1002/path.1570] [PMID: 15141377]
[46]
Salamanna, F.; Maglio, M.; Landini, M.P.; Fini, M. Body localization of ACE-2: On the trail of the keyhole of SARS-CoV-2. Front. Med. (Lausanne), 2020, 7, 594495.
[http://dx.doi.org/10.3389/fmed.2020.594495] [PMID: 33344479]
[47]
Zou, X.; Chen, K.; Zou, J.; Han, P.; Hao, J.; Han, Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med., 2020, 14(2), 185-192.
[http://dx.doi.org/10.1007/s11684-020-0754-0] [PMID: 32170560]
[48]
Liu, Y.; Wu, Q.; Wan, D.; He, H.; Lin, H.; Wang, K.; Que, G.; Wang, Y.; Chen, Y.; Tang, X.; Wu, L.; Yang, X. Expression and possible significance of ACE2 in the human liver, esophagus, stomach, and colon. Evid. Based Complement. Alternat. Med., 2021, 2021, 6949902.
[http://dx.doi.org/10.1155/2021/6949902] [PMID: 34484401]
[49]
Simões e Silva, A.C.; Silveira, K.D.; Ferreira, A.J.; Teixeira, M.M. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis. Br. J. Pharmacol., 2013, 169(3), 477-492.
[http://dx.doi.org/10.1111/bph.12159] [PMID: 23488800]
[50]
Li, X.C.; Zhang, J.; Zhuo, J.L. The vasoprotective axes of the reninangiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases. Pharmacol. Res. 2017, 125(Pt A), 21-38.
[http://dx.doi.org/10.1016/j.phrs.2017.06.005] [PMID: 28619367]
[51]
Glowacka, I.; Bertram, S.; Müller, M.A.; Allen, P.; Soilleux, E.; Pfefferle, S.; Steffen, I.; Tsegaye, T.S.; He, Y.; Gnirss, K.; Niemeyer, D.; Schneider, H.; Drosten, C.; Pöhlmann, S. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J. Virol., 2011, 85(9), 4122-4134.
[http://dx.doi.org/10.1128/JVI.02232-10] [PMID: 21325420]
[52]
Huang, Y.; Yang, C.; Xu, X.F.; Xu, W.; Liu, S.W. Structural and functional properties of SARS-CoV-2 spike protein: Potential antivirus drug development for COVID-19. Acta Pharmacol. Sin., 2020, 41(9), 1141-1149.
[http://dx.doi.org/10.1038/s41401-020-0485-4] [PMID: 32747721]
[53]
Ou, X.; Liu, Y.; Lei, X.; Li, P.; Mi, D.; Ren, L.; Guo, L.; Guo, R.; Chen, T.; Hu, J.; Xiang, Z.; Mu, Z.; Chen, X.; Chen, J.; Hu, K.; Jin, Q.; Wang, J.; Qian, Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun., 2020, 11(1), 1620.
[http://dx.doi.org/10.1038/s41467-020-15562-9] [PMID: 32221306]
[54]
Johnson, B.A.; Xie, X.; Kalveram, B.; Lokugamage, K.G.; Muruato, A.; Zou, J.; Zhang, X.; Juelich, T.; Smith, J.K.; Zhang, L. Furin cleavage site is key to SARS-CoV-2 pathogenesis. bioRxiv, 2020.
[http://dx.doi.org/10.1101/2020.08.26.268854]
[55]
Yang, J.; Chen, T.; Zhou, Y. Mediators of SARS-CoV-2 entry are preferentially enriched in cardiomyocytes. Hereditas, 2021, 158(1), 4.
[http://dx.doi.org/10.1186/s41065-020-00168-4] [PMID: 33397514]
[56]
Wang, D.; Hu, B.; Hu, C.; Zhu, F.; Liu, X.; Zhang, J.; Wang, B.; Xiang, H.; Cheng, Z.; Xiong, Y.; Zhao, Y.; Li, Y.; Wang, X.; Peng, Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020, 323(11), 1061-1069.
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[57]
Zhou, J.; Sun, J.; Cao, Z.; Wang, W.; Huang, K.; Zheng, F.; Xie, Y.; Jiang, D.; Zhou, Z. Epidemiological and clinical features of 201 COVID-19 patients in Changsha city, Hunan, China. Medicine (Baltimore), 2020, 99(34), e21824.
[http://dx.doi.org/10.1097/MD.0000000000021824] [PMID: 32846825]
[58]
Yu, C.; Lei, Q.; Li, W.; Wang, X.; Li, W.; Liu, W. Epidemiological and clinical characteristics of 1663 hospitalized patients infected with COVID-19 in Wuhan, China: A single-center experience. J. Infect. Public Health, 2020, 13(9), 1202-1209.
[http://dx.doi.org/10.1016/j.jiph.2020.07.002] [PMID: 32718894]
[59]
Zheng, Y.; Xiong, C.; Liu, Y.; Qian, X.; Tang, Y.; Liu, L.; Leung, E.L.H.; Wang, M. Epidemiological and clinical characteristics analysis of COVID-19 in the surrounding areas of Wuhan, Hubei Province in 2020. Pharmacol. Res., 2020, 157, 104821.
[http://dx.doi.org/10.1016/j.phrs.2020.104821] [PMID: 32360481]
[60]
Lauer, S.A.; Grantz, K.H.; Bi, Q.; Jones, F.K.; Zheng, Q.; Meredith, H.R.; Azman, A.S.; Reich, N.G.; Lessler, J. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: Estimation and application. Ann. Intern. Med., 2020, 172(9), 577-582.
[http://dx.doi.org/10.7326/M20-0504] [PMID: 32150748]
[61]
Zizza, A.; Recchia, V.; Aloisi, A.; Guido, M. Clinical features of COVID-19 and SARS epidemics. A literature review. J. Prev. Med. Hyg., 2021, 62(1), E13-E24.
[http://dx.doi.org/10.15167/2421-4248/jpmh2021.62.1.1680] [PMID: 34322612]
[62]
Mcgonagle, D.; Sharif, K.; Regan, A.O.; Bridgewood, C. The role of cytokines including IL-6 in COVID-19 induced pneumonia and MAS-like disease. Autoimmun. Rev., 2020, 19(6), 102537.
[http://dx.doi.org/10.1016/j.autrev.2020.102537] [PMID: 32251717]
[63]
Ye, Q.; Wang, B.; Mao, J. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J. Infect., 2020, 80(6), 607-613.
[http://dx.doi.org/10.1016/j.jinf.2020.03.037] [PMID: 32283152]
[64]
Kim, J.S.; Lee, J.Y.; Yang, J.W.; Lee, K.H.; Effenberger, M.; Szpirt, W.; Kronbichler, A.; Shin, J.I. Immunopathogenesis and treatment of cytokine storm in COVID-19. Theranostics, 2021, 11(1), 316-329.
[http://dx.doi.org/10.7150/thno.49713] [PMID: 33391477]
[65]
Chu, H.; Chan, J.F-W.; Wang, Y.; Yuen, T.T-T.; Chai, Y.; Hou, Y.; Shuai, H.; Yang, D.; Hu, B.; Huang, X.; Zhang, X.; Cai, J.P.; Zhou, J.; Yuan, S.; Kok, K.H.; To, K.K.; Chan, I.H.; Zhang, A.J.; Sit, K.Y.; Au, W.K.; Yuen, K.Y. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: An ex vivo study with implications for the pathogenesis of COVID-19. Clin. Infect. Dis., 2020, 71(6), 1400-1409.
[http://dx.doi.org/10.1093/cid/ciaa410] [PMID: 32270184]
[66]
Yuen, C.K.; Lam, J.Y.; Wong, W.M.; Mak, L.F.; Wang, X.; Chu, H.; Cai, J.P.; Jin, D.Y.; To, K.K.; Chan, J.F.; Yuen, K.Y.; Kok, K.H. SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists. Emerg. Microbes Infect., 2020, 9(1), 1418-1428.
[http://dx.doi.org/10.1080/22221751.2020.1780953] [PMID: 32529952]
[67]
Yang, D.; Chu, H.; Hou, Y.; Chai, Y.; Shuai, H.; Lee, A.C.Y.; Zhang, X.; Wang, Y.; Hu, B.; Huang, X.; Yuen, T.T.; Cai, J.P.; Zhou, J.; Yuan, S.; Zhang, A.J.; Chan, J.F.; Yuen, K.Y. Attenuated interferon and proinflammatory response in SARS-CoV-2-infected human dendritic cells is associated with viral antagonism of STAT1 phosphorylation. J. Infect. Dis., 2020, 222(5), 734-745.
[http://dx.doi.org/10.1093/infdis/jiaa356] [PMID: 32563187]
[68]
Channappanavar, R.; Perlman, S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol., 2017, 39(5), 529-539.
[http://dx.doi.org/10.1007/s00281-017-0629-x] [PMID: 28466096]
[69]
Merad, M.; Martin, J.C. Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages. Nat. Rev. Immunol., 2020, 20(6), 355-362.
[http://dx.doi.org/10.1038/s41577-020-0331-4] [PMID: 32376901]
[70]
Zhang, X.; Wu, K.; Wang, D.; Yue, X.; Song, D.; Zhu, Y.; Wu, J. Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB. Virology, 2007, 365(2), 324-335.
[http://dx.doi.org/10.1016/j.virol.2007.04.009] [PMID: 17490702]
[71]
Karwaciak, I. Sałkowska, A.; Karaś K.; Dastych, J.; Ratajewski, M. Nucleocapsid and spike proteins of the coronavirus SARS-CoV-2 Induce IL6 in monocytes and macrophages-potential implications for cytokine storm syndrome. Vaccines (Basel), 2021, 9(1), 54.
[http://dx.doi.org/10.3390/vaccines9010054] [PMID: 33467724]
[72]
Blot, M.; Jacquier, M.; Aho Glele, L.S.; Beltramo, G.; Nguyen, M.; Bonniaud, P.; Prin, S.; Andreu, P.; Bouhemad, B.; Bour, J.B.; Binquet, C.; Piroth, L.; Pais de Barros, J.P.; Masson, D.; Quenot, J.P.; Charles, P.E.; Aptel, F.; Dargent, A.; Georges, M.; Labruyère, M.; Lagrost, L.; Large, A.; Monier, S.; Roudaut, J-B.; Thomas, C. CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS. Crit. Care, 2020, 24(1), 632.
[http://dx.doi.org/10.1186/s13054-020-03328-0] [PMID: 33138839]
[73]
Feng, Z.; Diao, B.; Wang, R.; Wang, G.; Wang, C.; Tan, Y.; Liu, L.; Wang, C.; Liu, Y.; Liu, Y. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Directly decimates human spleens and lymph nodes. medRxiv, 2020.
[http://dx.doi.org/10.1101/2020.03.27.20045427]
[74]
Blanco-Melo, D.; Nilsson-Payant, B.E.; Liu, W-C.; Uhl, S.; Hoagland, D.; Møller, R.; Jordan, T.X.; Oishi, K.; Panis, M.; Sachs, D.; Wang, T.T.; Schwartz, R.E.; Lim, J.K.; Albrecht, R.A.; tenOever, B.R. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell, 2020, 181(5), 1036-1045.e9.
[http://dx.doi.org/10.1016/j.cell.2020.04.026] [PMID: 32416070]
[75]
Zhou, R.; To, K.K.W.; Wong, Y.C.; Liu, L.; Zhou, B.; Li, X.; Huang, H.; Mo, Y.; Luk, T.Y.; Lau, T.T.K.; Yeung, P.; Chan, W.M.; Wu, A.K.; Lung, K.C.; Tsang, O.T.; Leung, W.S.; Hung, I.F.; Yuen, K.Y.; Chen, Z. Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses. Immunity, 2020, 53(4), 864-877.e5.
[http://dx.doi.org/10.1016/j.immuni.2020.07.026] [PMID: 32791036]
[76]
Diao, B.; Wang, C.; Tan, Y.; Chen, X.; Liu, Y.; Ning, L.; Chen, L.; Li, M.; Liu, Y.; Wang, G.; Yuan, Z.; Feng, Z.; Zhang, Y.; Wu, Y.; Chen, Y. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front. Immunol., 2020, 11, 827.
[http://dx.doi.org/10.3389/fimmu.2020.00827] [PMID: 32425950]
[77]
Liang, X.; Giacomini, K.M. Transporters involved in metformin pharmacokinetics and treatment response. J. Pharm. Sci., 2017, 106(9), 2245-2250.
[http://dx.doi.org/10.1016/j.xphs.2017.04.078] [PMID: 28495567]
[78]
Owen, M.R.; Doran, E.; Halestrap, A.P. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J., 2000, 348(Pt 3), 607-614.
[http://dx.doi.org/10.1042/bj3480607] [PMID: 10839993]
[79]
Hirsch, A.; Hahn, D.; Kempná, P.; Hofer, G.; Nuoffer, J.M.; Mullis, P.E.; Flück, C.E. Metformin inhibits human androgen production by regulating steroidogenic enzymes HSD3B2 and CYP17A1 and complex I activity of the respiratory chain. Endocrinology, 2012, 153(9), 4354-4366.
[http://dx.doi.org/10.1210/en.2012-1145] [PMID: 22778212]
[80]
Wheaton, W.W.; Weinberg, S.E.; Hamanaka, R.B.; Soberanes, S.; Sullivan, L.B.; Anso, E.; Glasauer, A.; Dufour, E.; Mutlu, G.M.; Budigner, G.S.; Chandel, N.S. Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. eLife, 2014, 3, e02242.
[http://dx.doi.org/10.7554/eLife.02242] [PMID: 24843020]
[81]
Stephenne, X.; Foretz, M.; Taleux, N.; van der Zon, G.C.; Sokal, E.; Hue, L.; Viollet, B.; Guigas, B. Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia, 2011, 54(12), 3101-3110.
[http://dx.doi.org/10.1007/s00125-011-2311-5] [PMID: 21947382]
[82]
Alshawi, A.; Agius, L. Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism. J. Biol. Chem., 2019, 294(8), 2839-2853.
[http://dx.doi.org/10.1074/jbc.RA118.006670] [PMID: 30591586]
[83]
Woods, A.; Dickerson, K.; Heath, R.; Hong, S.P.; Momcilovic, M.; Johnstone, S.R.; Carlson, M.; Carling, D. Ca2+/calmodulin-dependent protein kinase kinase-β acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab., 2005, 2(1), 21-33.
[http://dx.doi.org/10.1016/j.cmet.2005.06.005] [PMID: 16054096]
[84]
Jensen, T.E.; Rose, A.J.; Jørgensen, S.B.; Brandt, N.; Schjerling, P.; Wojtaszewski, J.F.P.; Richter, E.A. Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction. Am. J. Physiol. Endocrinol. Metab., 2007, 292(5), E1308-E1317.
[http://dx.doi.org/10.1152/ajpendo.00456.2006] [PMID: 17213473]
[85]
Herrero-Martín, G.; Høyer-Hansen, M.; García-García, C.; Fumarola, C.; Farkas, T.; López-Rivas, A.; Jäättelä, M. TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. EMBO J., 2009, 28(6), 677-685.
[http://dx.doi.org/10.1038/emboj.2009.8] [PMID: 19197243]
[86]
Chen, Z.; Shen, X.; Shen, F.; Zhong, W.; Wu, H.; Liu, S.; Lai, J. TAK1 activates AMPK-dependent cell death pathway in hydrogen peroxide-treated cardiomyocytes, inhibited by heat shock protein-70. Mol. Cell. Biochem., 2013, 377(1-2), 35-44.
[http://dx.doi.org/10.1007/s11010-013-1568-z] [PMID: 23378049]
[87]
Joseph, B.K.; Liu, H.Y.; Francisco, J.; Pandya, D.; Donigan, M.; Gallo-Ebert, C.; Giordano, C.; Bata, A.; Nickels, J.T. Jr Inhibition of AMP kinase by the protein phosphatase 2A heterotrimer, PP2APpp2r2d. J. Biol. Chem., 2015, 290(17), 10588-10598.
[http://dx.doi.org/10.1074/jbc.M114.626259] [PMID: 25694423]
[88]
Davies, S.P.; Helps, N.R.; Cohen, P.T.W.; Hardie, D.G. 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C α and native bovine protein phosphatase-2AC. FEBS Lett., 1995, 377(3), 421-425.
[http://dx.doi.org/10.1016/0014-5793(95)01368-7] [PMID: 8549768]
[89]
Xiao, B.; Sanders, M.J.; Underwood, E.; Heath, R.; Mayer, F.V.; Carmena, D.; Jing, C.; Walker, P.A.; Eccleston, J.F.; Haire, L.F.; Saiu, P.; Howell, S.A.; Aasland, R.; Martin, S.R.; Carling, D.; Gamblin, S.J. Structure of mammalian AMPK and its regulation by ADP. Nature, 2011, 472(7342), 230-233.
[http://dx.doi.org/10.1038/nature09932] [PMID: 21399626]
[90]
Gowans, G.J.; Hawley, S.A.; Ross, F.A.; Hardie, D.G. AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab., 2013, 18(4), 556-566.
[http://dx.doi.org/10.1016/j.cmet.2013.08.019] [PMID: 24093679]
[91]
Jeon, S.M. Regulation and function of AMPK in physiology and diseases. Exp. Mol. Med., 2016, 48(7), e245.
[http://dx.doi.org/10.1038/emm.2016.81] [PMID: 27416781]
[92]
Madiraju, A.K.; Erion, D.M.; Rahimi, Y.; Zhang, X.M.; Braddock, D.T.; Albright, R.A.; Prigaro, B.J.; Wood, J.L.; Bhanot, S.; MacDonald, M.J.; Jurczak, M.J.; Camporez, J.P.; Lee, H.Y.; Cline, G.W.; Samuel, V.T.; Kibbey, R.G.; Shulman, G.I. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature, 2014, 510(7506), 542-546.
[http://dx.doi.org/10.1038/nature13270] [PMID: 24847880]
[93]
Madiraju, A.K.; Qiu, Y.; Perry, R.J.; Rahimi, Y.; Zhang, X.M.; Zhang, D.; Camporez, J.G.; Cline, G.W.; Butrico, G.M.; Kemp, B.E.; Casals, G.; Steinberg, G.R.; Vatner, D.F.; Petersen, K.F.; Shulman, G.I. Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nat. Med., 2018, 24(9), 1384-1394.
[http://dx.doi.org/10.1038/s41591-018-0125-4] [PMID: 30038219]
[94]
Straub, R.H.; Cutolo, M.; Buttgereit, F.; Pongratz, G. Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J. Intern. Med., 2010, 267(6), 543-560.
[http://dx.doi.org/10.1111/j.1365-2796.2010.02218.x] [PMID: 20210843]
[95]
Blumberg, D.; Hochwald, S.; Brennan, M.F.; Burt, M. Interleukin-6 stimulates gluconeogenesis in primary cultures of rat hepatocytes. Metabolism, 1995, 44(2), 145-146.
[http://dx.doi.org/10.1016/0026-0495(95)90255-4] [PMID: 7869907]
[96]
Zhang, W.; Mottillo, E.P.; Zhao, J.; Gartung, A.; VanHecke, G.C.; Lee, J.F.; Maddipati, K.R.; Xu, H.; Ahn, Y.H.; Proia, R.L.; Granneman, J.G.; Lee, M.J. Adipocyte lipolysis-stimulated interleukin-6 production requires sphingosine kinase 1 activity. J. Biol. Chem., 2014, 289(46), 32178-32185.
[http://dx.doi.org/10.1074/jbc.M114.601096] [PMID: 25253697]
[97]
Goodman, M.N. Tumor necrosis factor induces skeletal muscle protein breakdown in rats. Am. J. Physiol., 1991, 260(5 Pt 1), E727-E730.
[http://dx.doi.org/10.1152/ajpendo.1991.260.5.E727] [PMID: 2035628]
[98]
Goodman, M.N. Interleukin-6 induces skeletal muscle protein breakdown in rats. Proc. Soc. Exp. Biol. Med., 1994, 205(2), 182-185.
[http://dx.doi.org/10.3181/00379727-205-43695] [PMID: 8108469]
[99]
Li, P.; Yin, Y.L.; Li, D.; Kim, S.W.; Wu, G. Amino acids and immune function. Br. J. Nutr., 2007, 98(2), 237-252.
[http://dx.doi.org/10.1017/S000711450769936X] [PMID: 17403271]
[100]
Saxton, R.A.; Sabatini, D.M. mTOR signaling in growth, metabolism, and disease. Cell, 2017, 168(6), 960-976.
[http://dx.doi.org/10.1016/j.cell.2017.02.004] [PMID: 28283069]
[101]
Kiersztan, A.; Modzelewska, A.; Jarzyna, R.; Jagielska, E. Bryła, J. Inhibition of gluconeogenesis by vanadium and metformin in kidney-cortex tubules isolated from control and diabetic rabbits. Biochem. Pharmacol., 2002, 63(7), 1371-1382.
[http://dx.doi.org/10.1016/S0006-2952(02)00861-4] [PMID: 11960614]
[102]
Ren, T.; He, J.; Jiang, H.; Zu, L.; Pu, S.; Guo, X.; Xu, G. Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor necrosis factor-α or isoproterenol. J. Mol. Endocrinol., 2006, 37(1), 175-183.
[http://dx.doi.org/10.1677/jme.1.02061] [PMID: 16901933]
[103]
Grisouard, J.; Timper, K.; Bouillet, E.; Radimerski, T.; Dembinski, K.; Frey, D.M.; Peterli, R.; Zulewski, H.; Keller, U.; Müller, B.; Christ-Crain, M. Metformin counters both lipolytic/inflammatory agents-decreased hormone sensitive lipase phosphorylation at Ser-554 and -induced lipolysis in human adipocytes. Arch. Physiol. Biochem., 2011, 117(4), 209-214.
[http://dx.doi.org/10.3109/13813455.2010.550925] [PMID: 21338323]
[104]
Bhandari, S.; Rankawat, G.; Singh, A.; Gupta, V.; Kakkar, S. Impact of glycemic control in diabetes mellitus on management of COVID-19 infection. Int. J. Diabetes Dev. Ctries., 2020, 40(3), 1-6.
[http://dx.doi.org/10.1007/s13410-020-00868-7] [PMID: 32905072]
[105]
Logette, E.; Lorin, C.; Favreau, C.; Oshurko, E.; Coggan, J.S.; Casalegno, F.; Sy, M.F.; Monney, C.; Bertschy, M.; Delattre, E.; Fonta, P.A.; Krepl, J.; Schmidt, S.; Keller, D.; Kerrien, S.; Scantamburlo, E.; Kaufmann, A.K.; Markram, H. A machine-generated view of the role of blood glucose levels in the severity of COVID-19. Front. Public Health, 2021, 9, 695139.
[http://dx.doi.org/10.3389/fpubh.2021.695139] [PMID: 34395368]
[106]
Koepsell, H. The SLC22 family with transporters of organic cations, anions and zwitterions. Mol. Aspects Med., 2013, 34(2-3), 413-435.
[http://dx.doi.org/10.1016/j.mam.2012.10.010] [PMID: 23506881]
[107]
Berg, T.; Hegelund-Myrbäck, T.; Öckinger, J.; Zhou, X.H.; Brännström, M.; Hagemann-Jensen, M.; Werkström, V.; Seidegård, J.; Grunewald, J.; Nord, M.; Gustavsson, L. Expression of MATE1, P-gp, OCTN1 and OCTN2, in epithelial and immune cells in the lung of COPD and healthy individuals. Respir. Res., 2018, 19(1), 68.
[http://dx.doi.org/10.1186/s12931-018-0760-9] [PMID: 29678179]
[108]
Son, H.J.; Lee, J.; Lee, S.Y.; Kim, E.K.; Park, M.J.; Kim, K.W.; Park, S.H.; Cho, M.L. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis. Mediators Inflamm., 2014, 2014, 973986.
[http://dx.doi.org/10.1155/2014/973986] [PMID: 25214721]
[109]
Duan, W.; Ding, Y.; Yu, X.; Ma, D.; Yang, B.; Li, Y.; Huang, L.; Chen, Z.; Zheng, J.; Yang, C. Metformin mitigates autoimmune insulitis by inhibiting Th1 and Th17 responses while promoting Treg production. Am. J. Transl. Res., 2019, 11(4), 2393-2402.
[PMID: 31105845]
[110]
Kilberg, M.S.; Terada, N.; Shan, J. Influence of amino acid metabolism on embryonic stem cell function and differentiation. Adv. Nutr., 2016, 7(4), 780S-789S.
[http://dx.doi.org/10.3945/an.115.011031] [PMID: 27422515]
[111]
Kempkes, R.W.M.; Joosten, I.; Koenen, H.J.P.M.; He, X. Metabolic pathways involved in regulatory T cell functionality. Front. Immunol., 2019, 10, 2839.
[http://dx.doi.org/10.3389/fimmu.2019.02839] [PMID: 31849995]
[112]
Land, S.C.; Tee, A.R. Hypoxia-inducible factor 1α is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif. J. Biol. Chem., 2007, 282(28), 20534-20543.
[http://dx.doi.org/10.1074/jbc.M611782200] [PMID: 17502379]
[113]
Düvel, K.; Yecies, J.L.; Menon, S.; Raman, P.; Lipovsky, A.I.; Souza, A.L.; Triantafellow, E.; Ma, Q.; Gorski, R.; Cleaver, S.; Vander Heiden, M.G.; MacKeigan, J.P.; Finan, P.M.; Clish, C.B.; Murphy, L.O.; Manning, B.D. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol. Cell, 2010, 39(2), 171-183.
[http://dx.doi.org/10.1016/j.molcel.2010.06.022] [PMID: 20670887]
[114]
Zhao, Y.; Shao, Q.; Peng, G. Exhaustion and senescence: Two crucial dysfunctional states of T cells in the tumor microenvironment. Cell. Mol. Immunol., 2020, 17(1), 27-35.
[http://dx.doi.org/10.1038/s41423-019-0344-8] [PMID: 31853000]
[115]
Hurez, V.; Dao, V.; Liu, A.; Pandeswara, S.; Gelfond, J.; Sun, L.; Bergman, M.; Orihuela, C.J.; Galvan, V.; Padrón, Á.; Drerup, J.; Liu, Y.; Hasty, P.; Sharp, Z.D.; Curiel, T.J. Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate lymphoid cells and gut flora and prolongs life of immune-deficient mice. Aging Cell, 2015, 14(6), 945-956.
[http://dx.doi.org/10.1111/acel.12380] [PMID: 26315673]
[116]
Shin, S.; Hyun, B.; Lee, A.; Kong, H.; Han, S.; Lee, C.K.; Ha, N.J.; Kim, K. Metformin suppresses MHC-restricted antigen presentation by inhibiting co-stimulatory factors and MHC molecules in APCs. Biomol. Ther. (Seoul), 2013, 21(1), 35-41.
[http://dx.doi.org/10.4062/biomolther.2012.094] [PMID: 24009856]
[117]
Dai, X.; Bu, X.; Gao, Y.; Guo, J.; Hu, J.; Jiang, C.; Zhang, Z.; Xu, K.; Duan, J.; He, S.; Zhang, J.; Wan, L.; Liu, T.; Zhou, X.; Hung, M.C.; Freeman, G.J.; Wei, W. Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade. Mol. Cell, 2021, 81(11), 2317-2331.e6.
[http://dx.doi.org/10.1016/j.molcel.2021.03.037] [PMID: 33909988]
[118]
Cha, J.H.; Yang, W.H.; Xia, W.; Wei, Y.; Chan, L.C.; Lim, S.O.; Li, C.W.; Kim, T.; Chang, S.S.; Lee, H.H.; Hsu, J.L.; Wang, H.L.; Kuo, C.W.; Chang, W.C.; Hadad, S.; Purdie, C.A.; McCoy, A.M.; Cai, S.; Tu, Y.; Litton, J.K.; Mittendorf, E.A.; Moulder, S.L.; Symmans, W.F.; Thompson, A.M.; Piwnica-Worms, H.; Chen, C.H.; Khoo, K.H.; Hung, M.C. Metformin promotes antitumor immunity via endoplasmic-reticulum-associated degradation of PD-L1. Mol. Cell, 2018, 71(4), 606-620.e7.
[http://dx.doi.org/10.1016/j.molcel.2018.07.030] [PMID: 30118680]
[119]
Hu, C.; He, X.; Chen, Y.; Yang, X.; Qin, L.; Lei, T.; Zhou, Y.; Gong, T.; Huang, Y.; Gao, H. Metformin mediated PD-L1 downregulation in combination with photodynamic-immunotherapy for treatment of breast cancer. Adv. Funct. Mater., 2021, 31(11), 2007149.
[http://dx.doi.org/10.1002/adfm.202007149]
[120]
Sun, X.; Cui, Y.; Feng, H.; Liu, H.; Liu, X. TGF-β signaling controls Foxp3 methylation and T reg cell differentiation by modulating Uhrf1 activity. J. Exp. Med., 2019, 216(12), 2819-2837.
[http://dx.doi.org/10.1084/jem.20190550] [PMID: 31515281]
[121]
He, N.; Fan, W.; Henriquez, B.; Yu, R.T.; Atkins, A.R.; Liddle, C.; Zheng, Y.; Downes, M.; Evans, R.M. Metabolic control of regulatory T cell (Treg) survival and function by Lkb1. Proc. Natl. Acad. Sci. USA, 2017, 114(47), 12542-12547.
[http://dx.doi.org/10.1073/pnas.1715363114] [PMID: 29109251]
[122]
Sag, D.; Carling, D.; Stout, R.D.; Suttles, J. Adenosine 5′-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J. Immunol., 2008, 181(12), 8633-8641.
[http://dx.doi.org/10.4049/jimmunol.181.12.8633] [PMID: 19050283]
[123]
Ahmed, I.; Ismail, N. M1 and M2 macrophages polarization via mTORc1 influences innate immunity and outcome of Ehrlichia infection. J. Cell. Immunol., 2020, 2(3), 108-115.
[http://dx.doi.org/10.33696/immunology.2.029] [PMID: 32719831]
[124]
Qing, L.; Fu, J.; Wu, P.; Zhou, Z.; Yu, F.; Tang, J. Metformin induces the M2 macrophage polarization to accelerate the wound healing via regulating AMPK/mTOR/NLRP3 inflammasome singling pathway. Am. J. Transl. Res., 2019, 11(2), 655-668.
[PMID: 30899369]
[125]
Amoani, B.; Sakyi, S.A.; Mantey, R.; Laing, E.F.; Ephraim, R.D.; Sarfo-Katanka, O.; Koffie, S.; Obese, E.; Afranie, B.O. Increased metformin dosage suppresses pro-inflammatory cytokine levels in systemic circulation and might contribute to its beneficial effects. J. Immunoassay Immunochem., 2021, 42(3), 252-264.
[http://dx.doi.org/10.1080/15321819.2020.1862861] [PMID: 33444083]
[126]
Santos-Alvarez, J.; Goberna, R.; Sánchez-Margalet, V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell. Immunol., 1999, 194(1), 6-11.
[http://dx.doi.org/10.1006/cimm.1999.1490] [PMID: 10357875]
[127]
Martín-Romero, C.; Santos-Alvarez, J.; Goberna, R.; Sánchez-Margalet, V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell. Immunol., 2000, 199(1), 15-24.
[http://dx.doi.org/10.1006/cimm.1999.1594] [PMID: 10675271]
[128]
Procaccini, C.; De Rosa, V.; Galgani, M.; Carbone, F.; Cassano, S.; Greco, D.; Qian, K.; Auvinen, P.; Calì, G.; Stallone, G.; Formisano, L.; La Cava, A.; Matarese, G. Leptin-induced mTOR activation defines a specific molecular and transcriptional signature controlling CD4+ effector T cell responses. J. Immunol., 2012, 189(6), 2941-2953.
[http://dx.doi.org/10.4049/jimmunol.1200935] [PMID: 22904304]
[129]
van der Voort, P.H.J.; Moser, J.; Zandstra, D.F.; Muller Kobold, A.C.; Knoester, M.; Calkhoven, C.F.; Hamming, I.; van Meurs, M. Leptin levels in SARS-CoV-2 infection related respiratory failure: A cross-sectional study and a pathophysiological framework on the role of fat tissue. Heliyon, 2020, 6(8), e04696.
[http://dx.doi.org/10.1016/j.heliyon.2020.e04696] [PMID: 32844126]
[130]
Wang, J.; Xu, Y.; Zhang, X.; Wang, S.; Peng, Z.; Guo, J.; Jiang, H.; Liu, J.; Xie, Y.; Wang, J.; Li, X.; Liao, J.; Wan, C.; Yu, L.; Hu, J.; Liu, B.; Liu, Z. Leptin correlates with monocytes activation and severe condition in COVID-19 patients. J. Leukoc. Biol., 2021, 110(1), 9-20.
[http://dx.doi.org/10.1002/JLB.5HI1020-704R] [PMID: 33404078]
[131]
Mick, G.J.; Wang, X.; Ling, Fu C.; McCormick, K.L. Inhibition of leptin secretion by insulin and metformin in cultured rat adipose tissue. Biochim. Biophys. Acta, 2000, 1502(3), 426-432.
[http://dx.doi.org/10.1016/S0925-4439(00)00074-0] [PMID: 11068185]
[132]
Klein, J.; Westphal, S.; Kraus, D.; Meier, B.; Perwitz, N.; Ott, V.; Fasshauer, M.; Klein, H.H. Metformin inhibits leptin secretion via a mitogen-activated protein kinase signalling pathway in brown adipocytes. J. Endocrinol., 2004, 183(2), 299-307.
[http://dx.doi.org/10.1677/joe.1.05646] [PMID: 15531718]
[133]
Kim, Y.W.; Kim, J.Y.; Park, Y.H.; Park, S.Y.; Won, K.C.; Choi, K.H.; Huh, J.Y.; Moon, K.H. Metformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance. Diabetes, 2006, 55(3), 716-724.
[http://dx.doi.org/10.2337/diabetes.55.03.06.db05-0917] [PMID: 16505235]
[134]
Upadhyaya, P.; Rehan, H.S.; Seth, V. Serum leptin changes with metformin treatment in polycystic ovarian syndrome: Correlation with ovulation, insulin and testosterone levels. EXCLI J., 2011, 10, 9-15.
[http://dx.doi.org/10.17877/DE290R-1136] [PMID: 27857660]
[135]
Cai, H.; Dong, L.Q.; Liu, F. Recent advances in adipose mTOR signaling and function: Therapeutic prospects. Trends Pharmacol. Sci., 2016, 37(4), 303-317.
[http://dx.doi.org/10.1016/j.tips.2015.11.011] [PMID: 26700098]
[136]
Guo, Y.; Shi, J.; Wang, Q.; Hong, L.; Chen, M.; Liu, S.; Yuan, X.; Jiang, S. Metformin alleviates allergic airway inflammation and increases Treg cells in obese asthma. J. Cell. Mol. Med., 2021, 25(4), 2279-2284.
[http://dx.doi.org/10.1111/jcmm.16269] [PMID: 33421348]
[137]
Park, C.S.; Bang, B.R.; Kwon, H.S.; Moon, K.A.; Kim, T.B.; Lee, K.Y.; Moon, H.B.; Cho, Y.S. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase. Biochem. Pharmacol., 2012, 84(12), 1660-1670.
[http://dx.doi.org/10.1016/j.bcp.2012.09.025] [PMID: 23041647]
[138]
Brandtzaeg, P. Mucosal immunity: Induction, dissemination, and effector functions. Scand. J. Immunol., 2009, 70(6), 505-515.
[http://dx.doi.org/10.1111/j.1365-3083.2009.02319.x] [PMID: 19906191]
[139]
Blander, J.M.; Longman, R.S.; Iliev, I.D.; Sonnenberg, G.F.; Artis, D. Regulation of inflammation by microbiota interactions with the host. Nat. Immunol., 2017, 18(8), 851-860.
[http://dx.doi.org/10.1038/ni.3780] [PMID: 28722709]
[140]
Vignesh, R.; Swathirajan, C.R.; Tun, Z.H.; Rameshkumar, M.R.; Solomon, S.S.; Balakrishnan, P. Could perturbation of gut microbiota possibly exacerbate the severity of COVID-19 via cytokine storm? Front. Immunol., 2021, 11(January), 607734.
[http://dx.doi.org/10.3389/fimmu.2020.607734] [PMID: 33569053]
[141]
Zuo, T.; Zhang, F.; Lui, G.C.Y.; Yeoh, Y.K.; Li, A.Y.L.; Zhan, H.; Wan, Y.; Chung, A.C.K.; Cheung, C.P.; Chen, N.; Lai, C.K.C.; Chen, Z.; Tso, E.Y.K.; Fung, K.S.C.; Chan, V.; Ling, L.; Joynt, G.; Hui, D.S.C.; Chan, F.K.L.; Chan, P.K.S.; Ng, S.C. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology, 2020, 159(3), 944-955.e8.
[http://dx.doi.org/10.1053/j.gastro.2020.05.048] [PMID: 32442562]
[142]
de la Cuesta-Zuluaga, J.; Mueller, N.T.; Corrales-Agudelo, V.; Velásquez-Mejía, E.P.; Carmona, J.A.; Abad, J.M.; Escobar, J.S. Metformin is associated with higher relative abundance of mucin-degrading akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabetes Care, 2017, 40(1), 54-62.
[http://dx.doi.org/10.2337/dc16-1324] [PMID: 27999002]
[143]
Bryrup, T.; Thomsen, C.W.; Kern, T.; Allin, K.H.; Brandslund, I.; Jørgensen, N.R.; Vestergaard, H.; Hansen, T.; Hansen, T.H.; Pedersen, O.; Nielsen, T. Metformin-induced changes of the gut microbiota in healthy young men: Results of a non-blinded, one-armed intervention study. Diabetologia, 2019, 62(6), 1024-1035.
[http://dx.doi.org/10.1007/s00125-019-4848-7] [PMID: 30904939]
[144]
Elbere, I.; Kalnina, I.; Silamikelis, I.; Konrade, I.; Zaharenko, L.; Sekace, K.; Radovica-Spalvina, I.; Fridmanis, D.; Gudra, D.; Pirags, V.; Klovins, J. Association of metformin administration with gut microbiome dysbiosis in healthy volunteers. PLoS One, 2018, 13(9), e0204317.
[http://dx.doi.org/10.1371/journal.pone.0204317] [PMID: 30261008]
[145]
Tyagi, S.; Gupta, P.; Saini, A.S.; Kaushal, C.; Sharma, S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J. Adv. Pharm. Technol. Res., 2011, 2(4), 236-240.
[http://dx.doi.org/10.4103/2231-4040.90879] [PMID: 22247890]
[146]
Shintani, M.; Nishimura, H.; Yonemitsu, S.; Ogawa, Y.; Hayashi, T.; Hosoda, K.; Inoue, G.; Nakao, K. Troglitazone not only increases GLUT4 but also induces its translocation in rat adipocytes. Diabetes, 2001, 50(10), 2296-2300.
[http://dx.doi.org/10.2337/diabetes.50.10.2296] [PMID: 11574411]
[147]
Martinez, L.; Berenguer, M.; Bruce, M.C.; Le Marchand-Brustel, Y.; Govers, R. Rosiglitazone increases cell surface GLUT4 levels in 3T3-L1 adipocytes through an enhancement of endosomal recycling. Biochem. Pharmacol., 2010, 79(9), 1300-1309.
[http://dx.doi.org/10.1016/j.bcp.2009.12.013] [PMID: 20026082]
[148]
Standaert, M.L.; Kanoh, Y.; Sajan, M.P.; Bandyopadhyay, G.; Farese, R.V. Cbl, IRS-1, and IRS-2 mediate effects of rosiglitazone on PI3K, PKC-λ and glucose transport in 3T3/L1 adipocytes. Endocrinology, 2002, 143(5), 1705-1716.
[http://dx.doi.org/10.1210/endo.143.5.8812] [PMID: 11956152]
[149]
Hammarstedt, A.; Smith, U. Thiazolidinediones (PPARgamma ligands) increase IRS-1, UCP-2 and C/EBPalpha expression, but not transdifferentiation, in L6 muscle cells. Diabetologia, 2003, 46(1), 48-52.
[http://dx.doi.org/10.1007/s00125-002-1002-7] [PMID: 12637982]
[150]
Zhou, L.; Deepa, S.S.; Etzler, J.C.; Ryu, J.; Mao, X.; Fang, Q.; Liu, D.D.; Torres, J.M.; Jia, W.; Lechleiter, J.D.; Liu, F.; Dong, L.Q. Adiponectin activates AMP-activated protein kinase in muscle cells via APPL1/LKB1-dependent and phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathways. J. Biol. Chem., 2009, 284(33), 22426-22435.
[http://dx.doi.org/10.1074/jbc.M109.028357] [PMID: 19520843]
[151]
Yoon, Y.S.; Ryu, D.; Lee, M.W.; Hong, S.; Koo, S.H. Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis. Exp. Mol. Med., 2009, 41(8), 577-583.
[http://dx.doi.org/10.3858/emm.2009.41.8.063] [PMID: 19381067]
[152]
Ohashi, K.; Parker, J.L.; Ouchi, N.; Higuchi, A.; Vita, J.A.; Gokce, N.; Pedersen, A.A.; Kalthoff, C.; Tullin, S.; Sams, A.; Summer, R.; Walsh, K. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J. Biol. Chem., 2010, 285(9), 6153-6160.
[http://dx.doi.org/10.1074/jbc.M109.088708] [PMID: 20028977]
[153]
Lovren, F.; Pan, Y.; Quan, A.; Szmitko, P.E.; Singh, K.K.; Shukla, P.C.; Gupta, M.; Chan, L.; Al-Omran, M.; Teoh, H.; Verma, S. Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am. J. Physiol. Heart Circ. Physiol., 2010, 299(3), H656-H663.
[http://dx.doi.org/10.1152/ajpheart.00115.2010] [PMID: 20622108]
[154]
Ajuwon, K. M.; Spurlock, M. E. Adiponectin inhibits LPS-induced NF-KB activation and IL-6 production and increases PPARγ2 expression in adipocytes. Am. J. Physiol. - Regul. Integr. Comp. Physiol 2005, 288(5 57-5), 1220-1225.
[http://dx.doi.org/10.1152/ajpregu.00397.2004]
[155]
Chandrasekar, B.; Boylston, W.H.; Venkatachalam, K.; Webster, N.J.G.; Prabhu, S.D.; Valente, A.J. Adiponectin blocks interleukin-18-mediated endothelial cell death via APPL1-dependent AMP-activated protein kinase (AMPK) activation and IKK/NF-kappaB/PTEN suppression. J. Biol. Chem., 2008, 283(36), 24889-24898.
[http://dx.doi.org/10.1074/jbc.M804236200] [PMID: 18632660]
[156]
Kearns, S.M.; Ahern, K.W.; Patrie, J.T.; Horton, W.B.; Harris, T.E.; Kadl, A. Reduced adiponectin levels in patients with COVID-19 acute respiratory failure: A case-control study. Physiol. Rep., 2021, 9(7), e14843.
[http://dx.doi.org/10.14814/phy2.14843] [PMID: 33904656]
[157]
Di Filippo, L.; De Lorenzo, R.; Sciorati, C.; Capobianco, A.; Lorè, N.I.; Giustina, A.; Manfredi, A.A.; Rovere-Querini, P.; Conte, C. Adiponectin to leptin ratio reflects inflammatory burden and survival in COVID-19. Diabetes Metab., 2021, 47(6), 101268.
[http://dx.doi.org/10.1016/j.diabet.2021.101268] [PMID: 34333093]
[158]
El-Kurdi, B.; Khatua, B.; Rood, C.; Snozek, C.; Cartin-Ceba, R.; Singh, V.P.; El-Kurdi, B.; Khatua, B.; Rood, C.; Snozek, C.; Kostenko, S.; Trivedi, S.; Folmes, C.; Dykhouse, K.M.; Babar, S.; Chang, Y-H.; Pannala, R.; Cartin-Ceba, R.; Singh, V.P. Mortality from coronavirus disease 2019 increases with unsaturated fat and may be reduced by early calcium and albumin supplementation. Gastroenterology, 2020, 159(3), 1015-1018.e4.
[http://dx.doi.org/10.1053/j.gastro.2020.05.057] [PMID: 32470338]
[159]
Hegyi, P.; Szakács, Z.; Sahin-Tóth, M. Lipotoxicity and cytokine storm in severe acute pancreatitis and COVID-19. Gastroenterology, 2020, 159(3), 824-827.
[http://dx.doi.org/10.1053/j.gastro.2020.07.014] [PMID: 32682765]
[160]
Tordjman, J.; Chauvet, G.; Quette, J.; Beale, E.G.; Forest, C.; Antoine, B. Thiazolidinediones block fatty acid release by inducing glyceroneogenesis in fat cells. J. Biol. Chem., 2003, 278(21), 18785-18790.
[http://dx.doi.org/10.1074/jbc.M206999200] [PMID: 12644461]
[161]
He, J.; Xu, C.; Kuang, J.; Liu, Q.; Jiang, H.; Mo, L.; Geng, B.; Xu, G. Thiazolidinediones attenuate lipolysis and ameliorate dexamethasone-induced insulin resistance. Metabolism, 2015, 64(7), 826-836.
[http://dx.doi.org/10.1016/j.metabol.2015.02.005] [PMID: 25825274]
[162]
Boden, G.; Homko, C.; Mozzoli, M.; Showe, L.C.; Nichols, C.; Cheung, P. Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue of diabetic patients. Diabetes, 2005, 54(3), 880-885.
[http://dx.doi.org/10.2337/diabetes.54.3.880] [PMID: 15734868]
[163]
Medina-Gomez, G.; Gray, S. L.; Yetukuri, L.; Shimomura, K.; Virtue, S.; Campbell, M.; Curtis, R. K.; Jimenez-Linan, M.; Blount, M.; Yeo, G. S. H. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet, 2007, 3(4), 0634-0647.
[http://dx.doi.org/10.1371/journal.pgen.0030064]
[164]
Lee, Y.K.; Park, J.E.; Lee, M.; Hardwick, J.P. Hepatic lipid homeostasis by peroxisome proliferator-activated receptor gamma 2. Liver Res., 2018, 2(4), 209-215.
[http://dx.doi.org/10.1016/j.livres.2018.12.001] [PMID: 31245168]
[165]
Kaplan, J.; Nowell, M.; Chima, R.; Zingarelli, B. Pioglitazone reduces inflammation through inhibition of NF-κB in polymicrobial sepsis. Innate Immun., 2014, 20(5), 519-528.
[http://dx.doi.org/10.1177/1753425913501565] [PMID: 24029145]
[166]
Zhang, Y.F.; Zou, X.L. WU, J.; Yu, X.Q.; Yang, X. Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ agonist, attenuates inflammation via NF-KB inhibition in lipopolysaccharide-induced peritonitis. Inflammation, 2015, 38(6), 2105-2115.
[http://dx.doi.org/10.1007/s10753-015-0193-2] [PMID: 26047949]
[167]
Chima, R.S.; Hake, P.W.; Piraino, G.; Mangeshkar, P.; Denenberg, A.; Zingarelli, B. Ciglitazone ameliorates lung inflammation by modulating the inhibitor kappaB protein kinase/nuclear factor-kappaB pathway after hemorrhagic shock. Crit. Care Med., 2008, 36(10), 2849-2857.
[http://dx.doi.org/10.1097/CCM.0b013e318187810e] [PMID: 18828195]
[168]
Ricote, M.; Glass, C.K. PPARs and molecular mechanisms of transrepression. Biochim. Biophys. Acta, 2007, 1771(8), 926-935.
[http://dx.doi.org/10.1016/j.bbalip.2007.02.013] [PMID: 17433773]
[169]
Wang, W.; Zhu, Z.; Zhu, B.; Ma, Z. Peroxisome proliferator-activated receptor-gamma agonist induces regulatory T cells in a murine model of allergic rhinitis. Otolaryngol. Head Neck Surg., 2011, 144(4), 506-513.
[http://dx.doi.org/10.1177/0194599810396133] [PMID: 21493225]
[170]
Cipolletta, D.; Feuerer, M.; Li, A.; Kamei, N.; Lee, J.; Shoelson, S.E.; Benoist, C.; Mathis, D. PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature, 2012, 486(7404), 549-553.
[http://dx.doi.org/10.1038/nature11132] [PMID: 22722857]
[171]
Mancini, S.J.; Boyd, D.; Katwan, O.J.; Strembitska, A.; Almabrouk, T.A.; Kennedy, S.; Palmer, T.M.; Salt, I.P. Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms. Sci. Rep., 2018, 8(1), 1-14.
[http://dx.doi.org/10.1038/s41598-018-23420-4] [PMID: 29311619]
[172]
Lee, S.; Lee, D.Y. Glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes. Ann. Pediatr. Endocrinol. Metab., 2017, 22(1), 15-26.
[http://dx.doi.org/10.6065/apem.2017.22.1.15] [PMID: 28443255]
[173]
Hariyanto, T.I.; Intan, D.; Hananto, J.E.; Putri, C.; Kurniawan, A. Pre-admission glucagon-like peptide-1 receptor agonist (GLP-1RA) and mortality from coronavirus disease 2019 (Covid-19): A systematic review, meta-analysis, and meta-regression. Diabetes Res. Clin. Pract., 2021, 179, 109031.
[http://dx.doi.org/10.1016/j.diabres.2021.109031] [PMID: 34461139]
[174]
Huang, C.; Yuan, L.; Cao, S. Endogenous GLP-1 as a key self-defense molecule against lipotoxicity in pancreatic islets. Int. J. Mol. Med., 2015, 36(1), 173-185.
[http://dx.doi.org/10.3892/ijmm.2015.2207] [PMID: 25976560]
[175]
Yang, Y.; Lu, Y.; Han, F.; Chang, Y.; Li, X.; Han, Z.; Xue, M.; Cheng, Y.; Sun, B.; Chen, L. Saxagliptin regulates M1/M2 macrophage polarization via CaMKKβ/AMPK pathway to attenuate NAFLD. Biochem. Biophys. Res. Commun., 2018, 503(3), 1618-1624.
[http://dx.doi.org/10.1016/j.bbrc.2018.07.090] [PMID: 30060948]
[176]
Birnbaum, Y.; Bajaj, M.; Qian, J.; Ye, Y. Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3/ASC inflammasome. BMJ Open Diabetes Res. Care, 2016, 4(1), e000227.
[http://dx.doi.org/10.1136/bmjdrc-2016-000227] [PMID: 27547413]
[177]
Liu, Q.; Zhang, L.; Zhang, W.; Hao, Q.; Qiu, W.; Wen, Y.; Wang, H.; Li, X. Inhibition of NF-κB reduces renal inflammation and expression of PEPCK in type 2 diabetic Mice. Inflammation, 2018, 41(6), 2018-2029.
[http://dx.doi.org/10.1007/s10753-018-0845-0] [PMID: 30066289]
[178]
Longo, V.D.; Mattson, M.P. Fasting: Molecular mechanisms and clinical applications. Cell Metab., 2014, 19(2), 181-192.
[http://dx.doi.org/10.1016/j.cmet.2013.12.008] [PMID: 24440038]
[179]
Golbidi, S.; Daiber, A.; Korac, B.; Li, H.; Essop, M.F.; Laher, I. Health benefits of fasting and caloric restriction. Curr. Diab. Rep., 2017, 17(12), 123.
[http://dx.doi.org/10.1007/s11892-017-0951-7] [PMID: 29063418]
[180]
O’Carroll, S.M.; O’Neill, L.A.J. Targeting immunometabolism to treat COVID-19. Immunother. Adv., 2021, 1(1), b013.
[http://dx.doi.org/10.1093/immadv/ltab013] [PMID: 34240083]
[181]
Osuchowski, M.F.; Winkler, M.S.; Skirecki, T.; Cajander, S.; Shankar-Hari, M.; Lachmann, G.; Monneret, G.; Venet, F.; Bauer, M.; Brunkhorst, F.M.; Weis, S.; Garcia-Salido, A.; Kox, M.; Cavaillon, J.M.; Uhle, F.; Weigand, M.A.; Flohé, S.B.; Wiersinga, W.J.; Almansa, R.; de la Fuente, A.; Martin-Loeches, I.; Meisel, C.; Spinetti, T.; Schefold, J.C.; Cilloniz, C.; Torres, A.; Giamarellos-Bourboulis, E.J.; Ferrer, R.; Girardis, M.; Cossarizza, A.; Netea, M.G.; van der Poll, T.; Bermejo-Martín, J.F.; Rubio, I. The COVID-19 puzzle: Deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir. Med., 2021, 9(6), 622-642.
[http://dx.doi.org/10.1016/S2213-2600(21)00218-6] [PMID: 33965003]
[182]
Burns, J.S.; Manda, G. Metabolic pathways of the warburg effect in health and disease: Perspectives of choice, chain or chance. Int. J. Mol. Sci., 2017, 18(12), 1-28.
[http://dx.doi.org/10.3390/ijms18122755] [PMID: 29257069]
[183]
Soliman, S.; Faris, M.E.; Ratemi, Z.; Halwani, R. Switching host metabolism as an approach to dampen SARS-CoV-2 infection. Ann. Nutr. Metab., 2020, 76(5), 297-303.
[http://dx.doi.org/10.1159/000510508] [PMID: 32950986]
[184]
Gnoni, M.; Beas, R.; Vásquez-Garagatti, R. Is there any role of intermittent fasting in the prevention and improving clinical outcomes of COVID-19?: Intersection between inflammation, mTOR pathway, autophagy and calorie restriction. Virusdisease, 2021, 32(4), 1-10.
[http://dx.doi.org/10.1007/s13337-021-00703-5] [PMID: 34104708]
[185]
Mani, K.; Javaheri, A.; Diwan, A. Lysosomes mediate benefits of intermittent fasting in cardiometabolic disease: The janitor is the undercover boss. Compr. Physiol., 2018, 8(4), 1639-1667.
[http://dx.doi.org/10.1002/cphy.c180005] [PMID: 30215867]
[186]
Pehote, G.; Vij, N. Autophagy augmentation to alleviate immune response dysfunction, and resolve respiratory and COVID-19 exacerbations. Cells, 2020, 9(9), E1952.
[http://dx.doi.org/10.3390/cells9091952] [PMID: 32847034]
[187]
Arumugam, T.V.; Phillips, T.M.; Cheng, A.; Morrell, C.H.; Mattson, M.P.; Wan, R. Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann. Neurol., 2010, 67(1), 41-52.
[http://dx.doi.org/10.1002/ana.21798] [PMID: 20186857]

Rights & Permissions Print Cite
Article Metrics
6
© 2024 Bentham Science Publishers | Privacy Policy