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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Advances in Small Molecules of Flavonoids for the Regulation of Gluconeogenesis

Author(s): Xiaoran Wu, Aidong Wang, Chuchu Ning, Yangyang Wu and Sunhui Chen*

Volume 23, Issue 23, 2023

Published on: 07 August, 2023

Page: [2214 - 2231] Pages: 18

DOI: 10.2174/1568026623666230726145514

Price: $65

Abstract

Hyperglycemia resulting from over-gluconeogenesis is a prominent feature of type 2 diabetes mellitus (T2DM). Therefore, it is very important to reduce glucose output, especially liver glucose output, and maintain blood glucose homeostasis in the treatment of T2DM. It has been found that small molecules of natural flavonoids are able to act on various targets in the gluconeogenic pathways, interfering with rate-limiting enzyme activity or regulating the cascade of hormonal signaling and affecting all levels of transcription factors by limiting the transport of non-sugar substrates. As a result, gluconeogenesis is inhibited. Literature indicated that gluconeogenesis regulated by flavonoids could be divided into two pathways, namely the pre-translational pathway and the pro-translational pathway. The pre-translational pathway mainly interferes with the signaling pathway and transcription factors in gluconeogenesis and inhibits RNA transcription and the expression of gluconeogenic genes, while the post-translational pathway mainly regulates the transport of nonglucose substrates and directly inhibits four rate-limiting enzymes. This review describes the effects of small flavonoid molecules on different targets and signaling pathways during gluconeogenesis, as well as relevant validation methods, in the hope of providing references for similar studies and promoting the development of anti-diabetic drugs.

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[1]
Magnusson, I.; Rothman, D.L.; Katz, L.D.; Shulman, R.G.; Shulman, G.I. Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J. Clin. Invest., 1992, 90(4), 1323-1327.
[http://dx.doi.org/10.1172/JCI115997] [PMID: 1401068]
[2]
McAnuff, M.A.; Omoruyi, F.O.; Morrison, E.Y.S.A.; Asemota, H.N. Changes in some liver enzymes in streptozotocin-induced diabetic rats fed sapogenin extract from bitter yam (Dioscorea polygonoides) or commercial diosgenin. West Indian Med. J., 2005, 54(2), 97-101.
[http://dx.doi.org/10.1590/S0043-31442005000200002] [PMID: 15999877]
[3]
Yang, W.M.; Jeong, H.J.; Park, S.W.; Lee, W. Obesity-induced miR-15b is linked causally to the development of insulin resistance through the repression of the insulin receptor in hepatocytes. Mol. Nutr. Food Res., 2015, 59(11), 2303-2314.
[http://dx.doi.org/10.1002/mnfr.201500107] [PMID: 26179126]
[4]
Corssmit, E.P.M.; Romijn, J.A.; Sauerwein, H.P. Review article: Regulation of glucose production with special attention to nonclassical regulatory mechanisms: A review. Metabolism, 2001, 50(7), 742-755.
[http://dx.doi.org/10.1053/meta.2001.24195] [PMID: 11436176]
[5]
Klover, P.J.; Mooney, R.A. Hepatocytes: critical for glucose homeostasis. Int. J. Biochem. Cell Biol., 2004, 36(5), 753-758.
[http://dx.doi.org/10.1016/j.biocel.2003.10.002] [PMID: 15061128]
[6]
Groen, A.K.; van Roermund, C.W.; Vervoorn, R.C.; Tager, J.M. Control of gluconeogenesis in rat liver cells. Flux control coefficients of the enzymes in the gluconeogenic pathway in the absence and presence of glucagon. Biochem. J., 1986, 237(2), 379-389.
[http://dx.doi.org/10.1042/bj2370379] [PMID: 3800895]
[7]
Jitrapakdee, S.; St Maurice, M.; Rayment, I.; Cleland, W.W.; Wallace, J.C.; Attwood, P.V. Structure, mechanism and regulation of pyruvate carboxylase. Biochem. J., 2008, 413(3), 369-387.
[http://dx.doi.org/10.1042/BJ20080709] [PMID: 18613815]
[8]
Rines, A.K.; Sharabi, K.; Tavares, C.D.J.; Puigserver, P. Targeting hepatic glucose metabolism in the treatment of type 2 diabetes. Nat. Rev. Drug Discov., 2016, 15(11), 786-804.
[http://dx.doi.org/10.1038/nrd.2016.151] [PMID: 27516169]
[9]
Calderón-Montaño, J.M.; Burgos-Morón, E.; Pérez-Guerrero, C.; López-Lázaro, M. A review on the dietary flavonoid kaempferol. Mini Rev. Med. Chem., 2011, 11(4), 298-344.
[http://dx.doi.org/10.2174/138955711795305335] [PMID: 21428901]
[10]
Alkhalidy, H.; Moore, W.; Zhang, Y.; McMillan, R.; Wang, A.; Ali, M.; Suh, K.S.; Zhen, W.; Cheng, Z.; Jia, Z.; Hulver, M.; Liu, D. Small molecule kaempferol promotes insulin sensitivity and preserved pancreatic β -cell mass in middle-aged obese diabetic mice. J. Diabetes Res., 2015, 2015, 1-14.
[http://dx.doi.org/10.1155/2015/532984] [PMID: 26064984]
[11]
Alkhalidy, H.; Moore, W.; Wang, A.; Luo, J.; McMillan, R.P.; Wang, Y.; Zhen, W.; Hulver, M.W.; Liu, D. Kaempferol ameliorates hyperglycemia through suppressing hepatic gluconeogenesis and enhancing hepatic insulin sensitivity in diet-induced obese mice. J. Nutr. Biochem., 2018, 58, 90-101.
[http://dx.doi.org/10.1016/j.jnutbio.2018.04.014] [PMID: 29886193]
[12]
Qiao, W.; Zhao, C.; Qin, N.; Zhai, H.Y.; Duan, H.Q. Identification of trans-tiliroside as active principle with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinesis. J. Ethnopharmacol., 2011, 135(2), 515-521.
[http://dx.doi.org/10.1016/j.jep.2011.03.062] [PMID: 21463674]
[13]
Qin, N.; Chen, Y.; Jin, M.N.; Zhang, C.; Qiao, W.; Yue, X.L.; Duan, H.Q.; Niu, W.Y. Anti-obesity and anti-diabetic effects of flavonoid derivative (Fla-CN) via microRNA in high fat diet induced obesity mice. Eur. J. Pharm. Sci., 2016, 82, 52-63.
[http://dx.doi.org/10.1016/j.ejps.2015.11.013] [PMID: 26598088]
[14]
Qin, N.; Peng, L.Y.; Jin, M.N.; Wu, X.R.; Jia, M.; Gan, C.C.; Zhu, W.; Zhang, P.; Liu, X.Q.; Duan, H.Q. Target identification of anti-diabetic and anti-obesity flavonoid derivative (Fla-CN). Bioorg. Chem., 2022, 121, 105674.
[http://dx.doi.org/10.1016/j.bioorg.2022.105674] [PMID: 35182887]
[15]
Bricker, D.K.; Taylor, E.B.; Schell, J.C.; Orsak, T.; Boutron, A.; Chen, Y.C.; Cox, J.E.; Cardon, C.M.; Van Vranken, J.G.; Dephoure, N.; Redin, C.; Boudina, S.; Gygi, S.P.; Brivet, M.; Thummel, C.S.; Rutter, J. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science, 2012, 337(6090), 96-100.
[http://dx.doi.org/10.1126/science.1218099] [PMID: 22628558]
[16]
Constantin, R.P.; Constantin, R.P.; Bracht, A.; Yamamoto, N.S.; Ishii-Iwamoto, E.L.; Constantin, J. Molecular mechanisms of citrus flavanones on hepatic gluconeogenesis. Fitoterapia, 2014, 92, 148-162.
[http://dx.doi.org/10.1016/j.fitote.2013.11.003] [PMID: 24239748]
[17]
Rognstad, R. Rate-limiting steps in metabolic pathways. J. Biol. Chem., 1979, 254(6), 1875-1878.
[http://dx.doi.org/10.1016/S0021-9258(17)37738-4] [PMID: 422559]
[18]
She, P.; Burgess, S.C.; Shiota, M.; Flakoll, P.; Donahue, E.P.; Malloy, C.R.; Sherry, A.D.; Magnuson, M.A. Mechanisms by which liver-specific PEPCK knockout mice preserve euglycemia during starvation. Diabetes, 2003, 52(7), 1649-1654.
[http://dx.doi.org/10.2337/diabetes.52.7.1649] [PMID: 12829628]
[19]
Hakimi, P.; Johnson, M.T.; Yang, J.; Lepage, D.F.; Conlon, R.A.; Kalhan, S.C.; Reshef, L.; Tilghman, S.M.; Hanson, R.W. Phosphoenolpyruvate carboxykinase and the critical role of cataplerosis in the control of hepatic metabolism. Nutr. Metab. (Lond.), 2005, 2(1), 33.
[http://dx.doi.org/10.1186/1743-7075-2-33] [PMID: 16300682]
[20]
Marrero, J.; Rhee, K.Y.; Schnappinger, D.; Pethe, K.; Ehrt, S. Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection. Proc. Natl. Acad. Sci. USA, 2010, 107(21), 9819-9824.
[http://dx.doi.org/10.1073/pnas.1000715107] [PMID: 20439709]
[21]
Babu, P.V.A.; Liu, D.; Gilbert, E.R. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J. Nutr. Biochem., 2013, 24(11), 1777-1789.
[http://dx.doi.org/10.1016/j.jnutbio.2013.06.003] [PMID: 24029069]
[22]
Katiyar, S.P.; Jain, A.; Dhanjal, J.K.; Sundar, D. Mixed inhibition of cpepck by genistein, using an extended binding site located adjacent to its catalytic cleft. PLoS One, 2015, 10(11), e0141987.
[http://dx.doi.org/10.1371/journal.pone.0141987] [PMID: 26528723]
[23]
Dang, Q.; Kasibhatla, S.R.; Reddy, K.R.; Jiang, T.; Reddy, M.R.; Potter, S.C.; Fujitaki, J.M.; van Poelje, P.D.; Huang, J.; Lipscomb, W.N.; Erion, M.D. Discovery of potent and specific fructose-1,6-bisphosphatase inhibitors and a series of orally-bioavailable phosphoramidase-sensitive prodrugs for the treatment of type 2 diabetes. J. Am. Chem. Soc., 2007, 129(50), 15491-15502.
[http://dx.doi.org/10.1021/ja074871l] [PMID: 18041834]
[24]
Ke, H.; Liang, J.Y.; Zhang, Y.; Lipscomb, W.N. Conformational transition of fructose-1,6-bisphosphatase: structure comparison between the AMP complex (T form) and the fructose 6-phosphate complex (R form). Biochemistry, 1991, 30(18), 4412-4420.
[http://dx.doi.org/10.1021/bi00232a007] [PMID: 1850623]
[25]
Ke, H.M.; Zhang, Y.P.; Lipscomb, W.N. Crystal structure of fructose-1,6-bisphosphatase complexed with fructose 6-phosphate, AMP, and magnesium. Proc. Natl. Acad. Sci. USA, 1990, 87(14), 5243-5247.
[http://dx.doi.org/10.1073/pnas.87.14.5243] [PMID: 2164670]
[26]
Pontremoli, S.; Melloni, E.; Michetti, M.; Salamino, F.; Sparatore, B.; Horecker, B.L. On the mechanism of inhibition of fructose 1,6-bisphosphatase by fructose 2,6-bisphosphate. Arch. Biochem. Biophys., 1982, 218(2), 609-613.
[http://dx.doi.org/10.1016/0003-9861(82)90386-1] [PMID: 6297401]
[27]
Van Schaftingen, E.; Jett, M.F.; Hue, L.; Hers, H.G. Control of liver 6-phosphofructokinase by fructose 2,6-bisphosphate and other effectors. Proc. Natl. Acad. Sci. USA, 1981, 78(6), 3483-3486.
[http://dx.doi.org/10.1073/pnas.78.6.3483] [PMID: 6455662]
[28]
Proença, C.; Oliveira, A.; Freitas, M.; Ribeiro, D.; Sousa, J.L.C.; Ramos, M.J.; Silva, A.M.S.; Fernandes, P.A.; Fernandes, E. Structural specificity of flavonoids in the inhibition of human fructose 1,6-bisphosphatase. J. Nat. Prod., 2020, 83(5), 1541-1552.
[http://dx.doi.org/10.1021/acs.jnatprod.0c00014] [PMID: 32364726]
[29]
Zhang, Y.; Zhang, X.; Xiao, Z.; Zhang, X.; Sun, H. Hypoglycemic and hypolipidemic dual activities of extracts and flavonoids from Desmodium caudatum and an efficient synthesis of the most potent 8-prenylquercetin. Fitoterapia, 2022, 156, 105083.
[http://dx.doi.org/10.1016/j.fitote.2021.105083] [PMID: 34785238]
[30]
Alam, M.M.; Meerza, D.; Naseem, I. Protective effect of quercetin on hyperglycemia, oxidative stress and DNA damage in alloxan induced type 2 diabetic mice. Life Sci., 2014, 109(1), 8-14.
[http://dx.doi.org/10.1016/j.lfs.2014.06.005] [PMID: 24946265]
[31]
Harini, R.; Ezhumalai, M.; Pugalendi, K.V. Antihyperglycemic effect of biochanin A, a soy isoflavone, on streptozotocin-diabetic rats. Eur. J. Pharmacol., 2012, 676(1-3), 89-94.
[http://dx.doi.org/10.1016/j.ejphar.2011.11.051] [PMID: 22178203]
[32]
Argaud, D.; Zhang, Q.; Pan, W.; Maitra, S.; Pilkis, S.J.; Lange, A.J. Regulation of rat liver glucose-6-phosphatase gene expression in different nutritional and hormonal states: gene structure and 5′-flanking sequence. Diabetes, 1996, 45(11), 1563-1571.
[http://dx.doi.org/10.2337/diab.45.11.1563] [PMID: 8866562]
[33]
Nordlie, R.C.; Foster, J.D.; Lange, A.J. Regulation of glucose production by the liver. Annu. Rev. Nutr., 1999, 19(1), 379-406.
[http://dx.doi.org/10.1146/annurev.nutr.19.1.379] [PMID: 10448530]
[34]
Arion, W.J.; Lange, A.J.; Walls, H.E. Microsomal membrane integrity and the interactions of phlorizin with the glucose-6-phosphatase system. J. Biol. Chem., 1980, 255(21), 10387-10395.
[http://dx.doi.org/10.1016/S0021-9258(19)70477-3] [PMID: 6107297]
[35]
Guigas, B.; Naboulsi, R.; Villanueva, G.R.; Taleux, N.; Lopez-Novoa, J.M.; Leverve, X.M.; El-Mir, M.Y. The flavonoid silibinin decreases glucose-6-phosphate hydrolysis in perfused rat hepatocytes by an inhibitory effect on glucose-6-phosphatase. Cell. Physiol. Biochem., 2007, 20(6), 925-934.
[http://dx.doi.org/10.1159/000110453] [PMID: 17982275]
[36]
Csala, M.; Margittai, É.; Senesi, S.; Gamberucci, A.; Bánhegyi, G.; Mandl, J.; Benedetti, A. Inhibition of hepatic glucose 6-phosphatase system by the green tea flavanol epigallocatechin gallate. FEBS Lett., 2007, 581(8), 1693-1698.
[http://dx.doi.org/10.1016/j.febslet.2007.03.045] [PMID: 17412326]
[37]
Gonzalez-Mujica, F.; Motta, N.; Estrada, O.; Perdomo, E.; Méndez, J.; Hasegawa, M. Inhibition of hepatic neoglucogenesis and glucose-6-phosphatase by quercetin 3-O-α(2″-galloyl)rhamnoside isolated fromBauhinia megalandra leaves. Phytother. Res., 2005, 19(7), 624-627.
[http://dx.doi.org/10.1002/ptr.1704] [PMID: 16161025]
[38]
Estrada, O.; Hasegawa, M.; Gonzalez-Mujíca, F.; Motta, N.; Perdomo, E.; Solorzano, A.; Méndez, J.; Méndez, B.; Zea, E.G. Evaluation of flavonoids fromBauhinia megalandra leaves as inhibitors of glucose-6-phosphatase system. Phytother. Res., 2005, 19(10), 859-863.
[http://dx.doi.org/10.1002/ptr.1703] [PMID: 16261515]
[39]
Bruzual De Abreu, M.; Temraz, A.; Malafronte, N.; Gonzalez-Mujica, F.; Duque, S.; Braca, A. Phenolic derivatives from Ruprechtia polystachya and their inhibitory activities on the glucose-6-phosphatase system. Chem. Biodivers., 2011, 8(11), 2126-2134.
[http://dx.doi.org/10.1002/cbdv.201000334] [PMID: 22083925]
[40]
Mithieux, G.; Guignot, L.; Bordet, J.C.; Wiernsperger, N. Intrahepatic mechanisms underlying the effect of metformin in decreasing basal glucose production in rats fed a high-fat diet. Diabetes, 2002, 51(1), 139-143.
[http://dx.doi.org/10.2337/diabetes.51.1.139] [PMID: 11756333]
[41]
Saller, R.; Meier, R.; Brignoli, R. The use of silymarin in the treatment of liver diseases. Drugs, 2001, 61(14), 2035-2063.
[http://dx.doi.org/10.2165/00003495-200161140-00003] [PMID: 11735632]
[42]
Sivaccumar, J.P.; Leonardi, A.; Iaccarino, E.; Corvino, G.; Sanguigno, L.; Chambery, A.; Russo, R.; Valletta, M.; Latino, D.; Capasso, D.; Doti, N.; Ruvo, M.; Sandomenico, A. Development of a new highly selective monoclonal antibody against preferentially expressed antigen in melanoma (prame) and identification of the target epitope by bio-layer interferometry. Int. J. Mol. Sci., 2021, 22(6), 3166.
[http://dx.doi.org/10.3390/ijms22063166] [PMID: 33804612]
[43]
White, M.F. IRS proteins and the common path to diabetes. Am. J. Physiol. Endocrinol. Metab., 2002, 283(3), E413-E422.
[http://dx.doi.org/10.1152/ajpendo.00514.2001] [PMID: 12169433]
[44]
Cross, D.A.E.; Alessi, D.R.; Cohen, P.; Andjelkovich, M.; Hemmings, B.A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature, 1995, 378(6559), 785-789.
[http://dx.doi.org/10.1038/378785a0] [PMID: 8524413]
[45]
Franke, T.F.; Hornik, C.P.; Segev, L.; Shostak, G.A.; Sugimoto, C. PI3K/Akt and apoptosis: size matters. Oncogene, 2003, 22(56), 8983-8998.
[http://dx.doi.org/10.1038/sj.onc.1207115] [PMID: 14663477]
[46]
Cordero-Herrera, I.; Martín, M.A.; Bravo, L.; Goya, L.; Ramos, S. Cocoa flavonoids improve insulin signalling and modulate glucose production via AKT and AMPK in HepG2 cells. Mol. Nutr. Food Res., 2013, 57(6), 974-985.
[http://dx.doi.org/10.1002/mnfr.201200500] [PMID: 23456781]
[47]
Álvarez-Cilleros, D.; Martín, M.Á.; Ramos, S. (-)-epicatechin and the colonic 2,3-dihydroxybenzoic acid metabolite regulate glucose uptake, glucose production, and improve insulin signaling in renal nrk-52e cells. Mol. Nutr. Food Res., 2018, 62(4), 1700470.
[http://dx.doi.org/10.1002/mnfr.201700470] [PMID: 29205863]
[48]
Ali, M.Y.; Zaib, S.; Rahman, M.M.; Jannat, S.; Iqbal, J.; Park, S.K.; Chang, M.S. Didymin, a dietary citrus flavonoid exhibits anti-diabetic complications and promotes glucose uptake through the activation of PI3K/Akt signaling pathway in insulin-resistant HepG2 cells. Chem. Biol. Interact., 2019, 305, 180-194.
[http://dx.doi.org/10.1016/j.cbi.2019.03.018] [PMID: 30928401]
[49]
Elchebly, M.; Payette, P.; Michaliszyn, E.; Cromlish, W.; Collins, S.; Loy, A.L.; Normandin, D.; Cheng, A.; Himms-Hagen, J.; Chan, C.C.; Ramachandran, C.; Gresser, M.J.; Tremblay, M.L.; Kennedy, B.P. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science, 1999, 283(5407), 1544-1548.
[http://dx.doi.org/10.1126/science.283.5407.1544] [PMID: 10066179]
[50]
Salmeen, A.; Andersen, J.N.; Myers, M.P.; Tonks, N.K.; Barford, D. Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B. Mol. Cell, 2000, 6(6), 1401-1412.
[http://dx.doi.org/10.1016/S1097-2765(00)00137-4] [PMID: 11163213]
[51]
Chen, M.; Wang, K.; Zhang, Y.; Zhang, M.; Ma, Y.; Sun, H.; Jin, Z.; Zheng, H.; Jiang, H.; Yu, P.; Zhang, Y.; Sun, H. New insights into the biological activities of Chrysanthemum morifolium: Natural flavonoids alleviate diabetes by targeting α-glucosidase and the PTP-1B signaling pathway. Eur. J. Med. Chem., 2019, 178, 108-115.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.083] [PMID: 31176093]
[52]
Jiao, P.; Feng, B.; Li, Y.; He, Q.; Xu, H. Hepatic ERK activity plays a role in energy metabolism. Mol. Cell. Endocrinol., 2013, 375(1-2), 157-166.
[http://dx.doi.org/10.1016/j.mce.2013.05.021] [PMID: 23732116]
[53]
Zheng, Y.; Zhang, W.; Pendleton, E.; Leng, S.; Wu, J.; Chen, R.; Sun, X.J. Improved insulin sensitivity by calorie restriction is associated with reduction of ERK and p70S6K activities in the liver of obese Zucker rats. J. Endocrinol., 2009, 203(3), 337-347.
[http://dx.doi.org/10.1677/JOE-09-0181] [PMID: 19801385]
[54]
Lake, D.; Corrêa, S.A.L.; Müller, J. Negative feedback regulation of the ERK1/2 MAPK pathway. Cell. Mol. Life Sci., 2016, 73(23), 4397-4413.
[http://dx.doi.org/10.1007/s00018-016-2297-8] [PMID: 27342992]
[55]
Guo, J.; Chen, J.; Ren, W.; Zhu, Y.; Zhao, Q.; Zhang, K.; Su, D.; Qiu, C.; Zhang, W.; Li, K. Citrus flavone tangeretin is a potential insulin sensitizer targeting hepatocytes through suppressing MEK-ERK1/2 pathway. Biochem. Biophys. Res. Commun., 2020, 529(2), 277-282.
[http://dx.doi.org/10.1016/j.bbrc.2020.05.212] [PMID: 32703423]
[56]
Du, J.; Dong, Z.; Tan, L.; Tan, M.; Zhang, F.; Zhang, K.; Pan, G.; Li, C.; Shi, S.; Zhang, Y.; Liu, Y.; Cui, H. Tubeimoside i inhibits cell proliferation and induces a partly disrupted and cytoprotective autophagy through rapidly hyperactivation of mek1/2-erk1/2 cascade via promoting ptp1b in melanoma. Front. Cell Dev. Biol., 2020, 8, 607757.
[http://dx.doi.org/10.3389/fcell.2020.607757] [PMID: 33392197]
[57]
Jin, D.X.; He, J.F. Pi3k/akt signaling pathway–mediated three flavonoids’ modulation on glucose metabolism. Rev. Bras. Farmacogn., 2022, 32(5), 834-839.
[http://dx.doi.org/10.1007/s43450-022-00291-5]
[58]
Govorko, D.; Logendra, S.; Wang, Y.; Esposito, D.; Komarnytsky, S.; Ribnicky, D.; Poulev, A.; Wang, Z.; Cefalu, W.T.; Raskin, I. Polyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line. Am. J. Physiol. Endocrinol. Metab., 2007, 293(6), E1503-E1510.
[http://dx.doi.org/10.1152/ajpendo.00420.2007] [PMID: 17848630]
[59]
Liu, Y.; Qiu, Y.; Chen, Q.; Han, X.; Cai, M.; Hao, L. Puerarin suppresses the hepatic gluconeogenesis via activation of PI3K/Akt signaling pathway in diabetic rats and HepG2 cells. Biomed. Pharmacother., 2021, 137, 111325.
[http://dx.doi.org/10.1016/j.biopha.2021.111325] [PMID: 33761593]
[60]
Unger, R.H.; Cherrington, A.D. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J. Clin. Invest., 2012, 122(1), 4-12.
[http://dx.doi.org/10.1172/JCI60016] [PMID: 22214853]
[61]
Herzig, S.; Long, F.; Jhala, U.S.; Hedrick, S.; Quinn, R.; Bauer, A.; Rudolph, D.; Schutz, G.; Yoon, C.; Puigserver, P.; Spiegelman, B.; Montminy, M. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature, 2001, 413(6852), 179-183.
[http://dx.doi.org/10.1038/35093131] [PMID: 11557984]
[62]
Sharma, A.X.; Quittner-Strom, E.B.; Lee, Y.; Johnson, J.A.; Martin, S.A.; Yu, X.; Li, J.; Lu, J.; Cai, Z.; Chen, S.; Wang, M.; Zhang, Y.; Pearson, M.J.; Dorn, A.C.; McDonald, J.G.; Gordillo, R.; Yan, H.; Thai, D.; Wang, Z.V.; Unger, R.H.; Holland, W.L. Glucagon receptor antagonism improves glucose metabolism and cardiac function by promoting amp-mediated protein kinase in diabetic mice. Cell Rep., 2018, 22(7), 1760-1773.
[http://dx.doi.org/10.1016/j.celrep.2018.01.065] [PMID: 29444429]
[63]
Li, X.; Chen, Y.; Shen, J.Z.; Pan, Q.; Yang, W.; Yan, H.; Liu, H.; Ai, W.; Liao, W.; Guo, S. Epigallocatechin gallate inhibits hepatic glucose production in primary hepatocytes via downregulating pka signaling pathways and transcriptional factor foxo1. J. Agric. Food Chem., 2019, 67(13), 3651-3661.
[http://dx.doi.org/10.1021/acs.jafc.9b00395] [PMID: 30875211]
[64]
Francis, S.H.; Blount, M.A.; Corbin, J.D. Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol. Rev., 2011, 91(2), 651-690.
[http://dx.doi.org/10.1152/physrev.00030.2010] [PMID: 21527734]
[65]
Biddie, S.C.; Conway-Campbell, B.L.; Lightman, S.L. Dynamic regulation of glucocorticoid signalling in health and disease. Rheumatology (Oxford), 2012, 51(3), 403-412.
[http://dx.doi.org/10.1093/rheumatology/ker215] [PMID: 21891790]
[66]
Zhou, H.Y.; Hu, G.X.; Lian, Q.Q.; Morris, D.; Ge, R.S. The metabolism of steroids, toxins and drugs by 11β-hydroxysteroid dehydrogenase 1. Toxicology, 2012, 292(1), 1-12.
[http://dx.doi.org/10.1016/j.tox.2011.11.012] [PMID: 22154985]
[67]
Kotelevtsev, Y.; Holmes, M.C.; Burchell, A.; Houston, P.M.; Schmoll, D.; Jamieson, P.; Best, R.; Brown, R.; Edwards, C.R.W.; Seckl, J.R.; Mullins, J.J. 11β-Hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. Proc. Natl. Acad. Sci. USA, 1997, 94(26), 14924-14929.
[http://dx.doi.org/10.1073/pnas.94.26.14924] [PMID: 9405715]
[68]
Torres-Piedra, M.; Ortiz-Andrade, R.; Villalobos-Molina, R.; Singh, N.; Medina-Franco, J.L.; Webster, S.P.; Binnie, M.; Navarrete-Vázquez, G.; Estrada-Soto, S. A comparative study of flavonoid analogues on streptozotocin–nicotinamide induced diabetic rats: Quercetin as a potential antidiabetic agent acting via 11β-Hydroxysteroid dehydrogenase type 1 inhibition. Eur. J. Med. Chem., 2010, 45(6), 2606-2612.
[http://dx.doi.org/10.1016/j.ejmech.2010.02.049] [PMID: 20346546]
[69]
Zhu, Q.; Ge, F.; Dong, Y.; Sun, W.; Wang, Z.; Shan, Y.; Chen, R.; Sun, J.; Ge, R.S. Comparison of flavonoids and isoflavonoids to inhibit rat and human 11β-hydroxysteroid dehydrogenase 1 and 2. Steroids, 2018, 132, 25-32.
[http://dx.doi.org/10.1016/j.steroids.2018.01.013] [PMID: 29425740]
[70]
Minokoshi, Y.; Kim, Y.B.; Peroni, O.D.; Fryer, L.G.D.; Müller, C.; Carling, D.; Kahn, B.B. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature, 2002, 415(6869), 339-343.
[http://dx.doi.org/10.1038/415339a] [PMID: 11797013]
[71]
He, L.; Sabet, A.; Djedjos, S.; Miller, R.; Sun, X.; Hussain, M.A.; Radovick, S.; Wondisford, F.E. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell, 2009, 137(4), 635-646.
[http://dx.doi.org/10.1016/j.cell.2009.03.016] [PMID: 19450513]
[72]
Petersen, M.C.; Vatner, D.F.; Shulman, G.I. Regulation of hepatic glucose metabolism in health and disease. Nat. Rev. Endocrinol., 2017, 13(10), 572-587.
[http://dx.doi.org/10.1038/nrendo.2017.80] [PMID: 28731034]
[73]
Liu, Y.; Dentin, R.; Chen, D.; Hedrick, S.; Ravnskjaer, K.; Schenk, S.; Milne, J.; Meyers, D.J.; Cole, P.; Iii, J.Y.; Olefsky, J.; Guarente, L.; Montminy, M. A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature, 2008, 456(7219), 269-273.
[http://dx.doi.org/10.1038/nature07349] [PMID: 18849969]
[74]
Shaw, R.J.; Lamia, K.A.; Vasquez, D.; Koo, S.H.; Bardeesy, N.; DePinho, R.A.; Montminy, M.; Cantley, L.C. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science, 2005, 310(5754), 1642-1646.
[http://dx.doi.org/10.1126/science.1120781] [PMID: 16308421]
[75]
Kahn, B.B.; Alquier, T.; Carling, D.; Hardie, D.G. AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab., 2005, 1(1), 15-25.
[http://dx.doi.org/10.1016/j.cmet.2004.12.003] [PMID: 16054041]
[76]
Hardie, D.G.; Ross, F.A.; Hawley, S.A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol., 2012, 13(4), 251-262.
[http://dx.doi.org/10.1038/nrm3311] [PMID: 22436748]
[77]
Collins, Q.F.; Liu, H.Y.; Pi, J.; Liu, Z.; Quon, M.J.; Cao, W. Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, suppresses hepatic gluconeogenesis through 5′-AMP-activated protein kinase. J. Biol. Chem., 2007, 282(41), 30143-30149.
[http://dx.doi.org/10.1074/jbc.M702390200] [PMID: 17724029]
[78]
Hwang, J.T.; Park, I.J.; Shin, J.I.; Lee, Y.K.; Lee, S.K.; Baik, H.W.; Ha, J.; Park, O.J. Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem. Biophys. Res. Commun., 2005, 338(2), 694-699.
[http://dx.doi.org/10.1016/j.bbrc.2005.09.195] [PMID: 16236247]
[79]
Seo, W.D.; Lee, J.H.; Jia, Y.; Wu, C.; Lee, S.J. Saponarin activates AMPK in a calcium-dependent manner and suppresses gluconeogenesis and increases glucose uptake via phosphorylation of CRTC2 and HDAC5. Bioorg. Med. Chem. Lett., 2015, 25(22), 5237-5242.
[http://dx.doi.org/10.1016/j.bmcl.2015.09.057] [PMID: 26471090]
[80]
Jia, Y.; Wu, C.; Rivera-Piza, A.; Kim, Y.J.; Lee, J.H.; Lee, S.J. Mechanism of action of cyanidin 3-o-glucoside in gluconeogenesis and oxidative stress-induced cancer cell senescence. Antioxidants, 2022, 11(4), 749.
[http://dx.doi.org/10.3390/antiox11040749] [PMID: 35453434]
[81]
Talagavadi, V.; Rapisarda, P.; Galvano, F.; Pelicci, P.; Giorgio, M. Cyanidin-3- O -β-glucoside and protocatechuic acid activate AMPK/mTOR/S6K pathway and improve glucose homeostasis in mice. J. Funct. Foods, 2016, 21, 338-348.
[http://dx.doi.org/10.1016/j.jff.2015.12.007]
[82]
Housley, M.P.; Udeshi, N.D.; Rodgers, J.T.; Shabanowitz, J.; Puigserver, P.; Hunt, D.F.; Hart, G.W.A. PGC-1alpha-O-GlcNAc transferase complex regulates FoxO transcription factor activity in response to glucose. J. Biol. Chem., 2009, 284(8), 5148-5157.
[http://dx.doi.org/10.1074/jbc.M808890200] [PMID: 19103600]
[83]
Hawley, S.A.; Boudeau, J.; Reid, J.L.; Mustard, K.J.; Udd, L.; Mäkelä, T.P.; Alessi, D.R.; Hardie, D.G. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J. Biol., 2003, 2(4), 28.
[http://dx.doi.org/10.1186/1475-4924-2-28] [PMID: 14511394]
[84]
El-Mir, M.Y.; Nogueira, V.; Fontaine, E.; Avéret, N.; Rigoulet, M.; Leverve, X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J. Biol. Chem., 2000, 275(1), 223-228.
[http://dx.doi.org/10.1074/jbc.275.1.223] [PMID: 10617608]
[85]
Zhou, G.; Myers, R.; Li, Y.; Chen, Y.; Shen, X.; Fenyk-Melody, J.; Wu, M.; Ventre, J.; Doebber, T.; Fujii, N.; Musi, N.; Hirshman, M.F.; Goodyear, L.J.; Moller, D.E. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest., 2001, 108(8), 1167-1174.
[http://dx.doi.org/10.1172/JCI13505] [PMID: 11602624]
[86]
Qin, N.; Li, C.B.; Jin, M.N.; Shi, L.H.; Duan, H.Q.; Niu, W.Y. Synthesis and biological activity of novel tiliroside derivants. Eur. J. Med. Chem., 2011, 46(10), 5189-5195.
[http://dx.doi.org/10.1016/j.ejmech.2011.07.059] [PMID: 21856048]
[87]
Turner, N.; Li, J.Y.; Gosby, A.; To, S.W.C.; Cheng, Z.; Miyoshi, H.; Taketo, M.M.; Cooney, G.J.; Kraegen, E.W.; James, D.E.; Hu, L.H.; Li, J.; Ye, J.M. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes, 2008, 57(5), 1414-1418.
[http://dx.doi.org/10.2337/db07-1552] [PMID: 18285556]
[88]
Xu, M.; Xiao, Y.; Yin, J.; Hou, W.; Yu, X.; Shen, L.; Liu, F.; Wei, L.; Jia, W. Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. PLoS One, 2014, 9(7), e103702.
[http://dx.doi.org/10.1371/journal.pone.0103702] [PMID: 25072399]
[89]
Hou, W.L.; Yin, J.; Alimujiang, M.; Yu, X.Y.; Ai, L.G.; Bao, Y.; Liu, F.; Jia, W.P. Inhibition of mitochondrial complex I improves glucose metabolism independently of AMPK activation. J. Cell. Mol. Med., 2017, 22(2), 1316-1328.
[http://dx.doi.org/10.1111/jcmm.13432] [PMID: 29106036]
[90]
Miller, R.A.; Chu, Q.; Xie, J.; Foretz, M.; Viollet, B.; Birnbaum, M.J. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature, 2013, 494(7436), 256-260.
[http://dx.doi.org/10.1038/nature11808] [PMID: 23292513]
[91]
Rong, X.; Sun-Waterhouse, D.; Wang, D.; Jiang, Y.; Li, F.; Chen, Y.; Zhao, S.; Li, D. The significance of regulatory micrornas: Their roles in toxicodynamics of mycotoxins and in the protection offered by dietary therapeutics against mycotoxin-induced toxicity. Compr. Rev. Food Sci. Food Saf., 2019, 18(1), 48-66.
[http://dx.doi.org/10.1111/1541-4337.12412] [PMID: 33337015]
[92]
Aryal, B.; Singh, A.K.; Rotllan, N.; Price, N.; Fernández-Hernando, C. MicroRNAs and lipid metabolism. Curr. Opin. Lipidol., 2017, 28(3), 273-280.
[http://dx.doi.org/10.1097/MOL.0000000000000420] [PMID: 28333713]
[93]
Yang, W.M.; Min, K.H.; Park, S.W.; Lee, W. Data on the expression of PEPCK in HepG2 hepatocytes transfected with miR-195. Data Brief, 2017, 15, 747-751.
[http://dx.doi.org/10.1016/j.dib.2017.10.061] [PMID: 29159212]
[94]
Liu, H.; Guan, H.; Tan, X.; Jiang, Y.; Li, F.; Sun-Waterhouse, D.; Li, D. Enhanced alleviation of insulin resistance via the IRS-1/Akt/FOXO1 pathway by combining quercetin and EGCG and involving miR-27a-3p and miR-96–5p. Free Radic. Biol. Med., 2022, 181, 105-117.
[http://dx.doi.org/10.1016/j.freeradbiomed.2022.02.002] [PMID: 35124182]
[95]
Yang, W.M.; Jeong, H.J.; Park, S.Y.; Lee, W. Saturated fatty acid-induced miR-195 impairs insulin signaling and glycogen metabolism in HepG2 cells. FEBS Lett., 2014, 588(21), 3939-3946.
[http://dx.doi.org/10.1016/j.febslet.2014.09.006] [PMID: 25240198]
[96]
Chakraborty, C.; Doss, C.G.P.; Bandyopadhyay, S.; Agoramoorthy, G. Influence of MIRNA in insulin signaling pathway and insulin resistance: micro‐molecules with a major role in type‐2 diabetes. Wiley Interdiscip. Rev. RNA, 2014, 5(5), 697-712.
[http://dx.doi.org/10.1002/wrna.1240] [PMID: 24944010]
[97]
Li, X. miR-375, a microRNA related to diabetes. Gene, 2014, 533(1), 1-4.
[http://dx.doi.org/10.1016/j.gene.2013.09.105] [PMID: 24120394]
[98]
Wu, Y.; Pan, Q.; Yan, H.; Zhang, K.; Guo, X.; Xu, Z.; Yang, W.; Qi, Y.; Guo, C.A.; Hornsby, C.; Zhang, L.; Zhou, A.; Li, L.; Chen, Y.; Zhang, W.; Sun, Y.; Zheng, H.; Wondisford, F.; He, L.; Guo, S. Novel mechanism of foxo1 phosphorylation in glucagon signaling in control of glucose homeostasis. Diabetes, 2018, 67(11), 2167-2182.
[http://dx.doi.org/10.2337/db18-0674] [PMID: 30201683]
[99]
Lin, H.V.; Accili, D. Hormonal regulation of hepatic glucose production in health and disease. Cell Metab., 2011, 14(1), 9-19.
[http://dx.doi.org/10.1016/j.cmet.2011.06.003] [PMID: 21723500]
[100]
Damayanti, D.S.; Utomo, D.H.; Kusuma, C. Revealing the potency of Annona muricata leaves extract as FOXO1 inhibitor for diabetes mellitus treatment through computational study. In Silico Pharmacol., 2017, 5(1), 3.
[http://dx.doi.org/10.1007/s40203-017-0023-3] [PMID: 28653156]
[101]
Davella, R.; Mamidala, E. Molecular docking of flavonoids from rumex vesicarius with foxo1 target related to diabetes mellitus. Biolife, 2019, 7(4), 7-13.
[http://dx.doi.org/10.17812/blj.2019.7402]
[102]
Ho, C.Y.; Cheng, Y.T.; Chau, C.F.; Yen, G.C. Effect of diallyl sulfide on in vitro and in vivo Nrf2-mediated pulmonic antioxidant enzyme expression via activation ERK/p38 signaling pathway. J. Agric. Food Chem., 2012, 60(1), 100-107.
[http://dx.doi.org/10.1021/jf203800d] [PMID: 22118872]
[103]
Heiss, E.H.; Schachner, D.; Zimmermann, K.; Dirsch, V.M. Glucose availability is a decisive factor for Nrf2-mediated gene expression. Redox Biol., 2013, 1(1), 359-365.
[http://dx.doi.org/10.1016/j.redox.2013.06.001] [PMID: 24024172]
[104]
Aleksunes, L.M.; Reisman, S.A.; Yeager, R.L.; Goedken, M.J.; Klaassen, C.D. Nuclear factor erythroid 2-related factor 2 deletion impairs glucose tolerance and exacerbates hyperglycemia in type 1 diabetic mice. J. Pharmacol. Exp. Ther., 2010, 333(1), 140-151.
[http://dx.doi.org/10.1124/jpet.109.162271] [PMID: 20086057]
[105]
Slocum, S.L.; Skoko, J.J.; Wakabayashi, N.; Aja, S.; Yamamoto, M.; Kensler, T.W.; Chartoumpekis, D.V. Keap1/Nrf2 pathway activation leads to a repressed hepatic gluconeogenic and lipogenic program in mice on a high-fat diet. Arch. Biochem. Biophys., 2016, 591, 57-65.
[http://dx.doi.org/10.1016/j.abb.2015.11.040] [PMID: 26701603]
[106]
Bumke-Vogt, C.; Osterhoff, M.A.; Borchert, A.; Guzman-Perez, V.; Sarem, Z.; Birkenfeld, A.L.; Bähr, V.; Pfeiffer, A.F.H. The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells. PLoS One, 2014, 9(8), e104321.
[http://dx.doi.org/10.1371/journal.pone.0104321] [PMID: 25136826]
[107]
Kwok, R.P.S.; Laurance, M.E.; Lundblad, J.R.; Goldman, P.S.; Shih, H.; Connor, L.M.; Marriott, S.J.; Goodman, R.H. Control of cAMP-regulated enhancers by the viral transactivator Tax through CREB and the co-activator CBP. Nature, 1996, 380(6575), 642-646.
[http://dx.doi.org/10.1038/380642a0] [PMID: 8602268]
[108]
Zhang, M.; Lv, X.; Li, J.; Meng, Z.; Wang, Q.; Chang, W.; Li, W.; Chen, L.; Liu, Y. Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis. Mol. Cell. Endocrinol., 2012, 363(1-2), 122-130.
[http://dx.doi.org/10.1016/j.mce.2012.08.006] [PMID: 22922125]
[109]
Besseiche, A.; Riveline, J.P.; Gautier, J.F.; Bréant, B.; Blondeau, B. Metabolic roles of PGC-1α and its implications for type 2 diabetes. Diabetes Metab., 2015, 41(5), 347-357.
[http://dx.doi.org/10.1016/j.diabet.2015.02.002] [PMID: 25753246]
[110]
Dal Piaz, F.; Vera Saltos, M.B.; Franceschelli, S.; Forte, G.; Marzocco, S.; Tuccinardi, T.; Poli, G.; Nejad Ebrahimi, S.; Hamburger, M.; De Tommasi, N.; Braca, A. Drug affinity responsive target stability (darts) identifies laurifolioside as a new clathrin heavy chain modulator. J. Nat. Prod., 2016, 79(10), 2681-2692.
[http://dx.doi.org/10.1021/acs.jnatprod.6b00627] [PMID: 27704815]
[111]
Roberts, J.H.; Liu, F.; Karnuta, J.M.; Fitzgerald, M.C. Discovery of age-related protein folding stability differences in the mouse brain proteome. J. Proteome Res., 2016, 15(12), 4731-4741.
[http://dx.doi.org/10.1021/acs.jproteome.6b00927] [PMID: 27806573]
[112]
Cohen, R.; Orlova, Y.; Kovalev, M.; Ungar, Y.; Shimoni, E. Structural and functional properties of amylose complexes with genistein. J. Agric. Food Chem., 2008, 56(11), 4212-4218.
[http://dx.doi.org/10.1021/jf800255c] [PMID: 18489110]
[113]
Shulman, M.; Cohen, M.; Soto-Gutierrez, A.; Yagi, H.; Wang, H.; Goldwasser, J.; Lee-Parsons, C.W.; Benny-Ratsaby, O.; Yarmush, M.L.; Nahmias, Y. Enhancement of naringenin bioavailability by complexation with hydroxypropyl-β-cyclodextrin. [corrected]. PLoS One, 2011, 6(4), e18033.
[http://dx.doi.org/10.1371/journal.pone.0018033] [PMID: 21494673]
[114]
Mohan, S.; Nandhakumar, L. Role of various flavonoids: Hypotheses on novel approach to treat diabetes. Journal of Medical Hypotheses and Ideas, 2014, 8(1), 1-6.
[http://dx.doi.org/10.1016/j.jmhi.2013.06.001]

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