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Endocrine, Metabolic & Immune Disorders - Drug Targets

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

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Research Article

Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells

Author(s): Xiuhong Lin*, Lin Cheng*, Yan Wan, Yuerong Yan, Zhuo Zhang, Xiaohui Li, Jiayun Wu, Xiaoyi Wang and Mingtong Xu

Volume 23, Issue 9, 2023

Published on: 24 February, 2023

Page: [1186 - 1200] Pages: 15

DOI: 10.2174/1871530323666230206121715

Price: $65

Abstract

Background: The RAS system is involved in the regulation of islet function, but its regulation remains unclear.

Objective: This study investigates the role of an islet-specific miR-375 in the effect of RAS system on islet β-cells.

Methods: miR-375 mimics and inhibitors were transfected into insulin-secreting MIN6 cells in the presence or absence of RAS component.

Results: Compared to control, in Ang II-treated MIN6 cells, miR-375 mimic transfection results in a decrement in cell viability and Akt-Ser levels (0.739±0.05 vs. 0.883±0.06 and 0.40±0.04 vs. 0.79±0.04, respectively), while the opposite occurred in miR-375 inhibitor-transfected cells (1.032±0.11 vs. 0.883±0.06 and 0.98±0.05 vs. 0.79±0.04, respectively, P<0.05). Mechanistically, transfection of miR- 375 mimics into Ang II-treated MIN6 cells significantly reduced the expression of Mapkap1 protein (0.97±0.15 vs. 0.63±0.06, P<0.05); while miR-375 inhibitor-transfected cells elevated Mapkap1 expression level (0.35±0.11 vs. 0.90±0.05, P<0.05), without changes in mRNA expression. Transfection of miR-375 specific inhibitors TSB-Mapkap1 could elevate Mapkap1 (1.62±0.02 vs. 0.68±0.01, P<0.05), while inhibition of Mapkap1 could significantly reduce the level of Akt-Ser473 phosphorylation (0.60±0.14 vs. 1.80±0.27, P<0.05).

Conclusion: The effects of Ang II on mouse islet β cells were mediated by miR-375 through miR- 375/Mapkap 1 axis. This targeted regulation may occur by affecting Akt phosphorylation of β cells. These results may provide new ideas and a scientific basis for further development of miRNA-targeted islet protection measures.

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[1]
Ogurtsova, K.; Guariguata, L.; Barengo, N.C.; Ruiz, P.L.D.; Sacre, J.W.; Karuranga, S.; Sun, H.; Boyko, E.J.; Magliano, D.J. IDF diabetes Atlas: Global estimates of undiagnosed diabetes in adults for 2021. Diabetes Res. Clin. Pract., 2022, 183, 109118.
[http://dx.doi.org/10.1016/j.diabres.2021.109118] [PMID: 34883189]
[2]
Joglekar, M.V.; Parekh, V.S.; Hardikar, A.A. Islet-specific microRNAs in pancreas development, regeneration and diabetes. Indian J. Exp. Biol., 2011, 49(6), 401-408.
[PMID: 21702218]
[3]
Walker, J.T.; Saunders, D.C.; Brissova, M.; Powers, A.C. The human islet: mini-organ with mega-impact. Endocr. Rev., 2021, 42(5), 605-657.
[http://dx.doi.org/10.1210/endrev/bnab010] [PMID: 33844836]
[4]
Elghazi, L.; Bernal-Mizrachi, E. Akt and PTEN: β-cell mass and pancreas plasticity. Trends Endocrinol. Metab., 2009, 20(5), 243-251.
[http://dx.doi.org/10.1016/j.tem.2009.03.002] [PMID: 19541499]
[5]
Assmann, A.; Hinault, C.; Kulkarni, R.N. Growth factor control of pancreatic islet regeneration and function. Pediatr. Diabetes, 2009, 10(1), 14-32.
[http://dx.doi.org/10.1111/j.1399-5448.2008.00468.x] [PMID: 18828795]
[6]
Muller, D.; Huang, G.C.; Amiel, S.; Jones, P.M.; Persaud, S.J. Identification of insulin signaling elements in human beta-cells: Autocrine regulation of insulin gene expression. Diabetes, 2006, 55(10), 2835-2842.
[http://dx.doi.org/10.2337/db06-0532] [PMID: 17003350]
[7]
Mallat, S.G. Dual renin-angiotensin system inhibition for prevention of renal and cardiovascular events: do the latest trials challenge existing evidence? Cardiovasc. Diabetol., 2013, 12(1), 108.
[http://dx.doi.org/10.1186/1475-2840-12-108] [PMID: 23866091]
[8]
Cheng, Q.; Leung, P.S. An update on the islet renin–angiotensin system. Peptides, 2011, 32(5), 1087-1095.
[http://dx.doi.org/10.1016/j.peptides.2011.03.003] [PMID: 21396973]
[9]
Luther, J.M.; Brown, N.J. The renin–angiotensin–aldosterone system and glucose homeostasis. Trends Pharmacol. Sci., 2011, 32(12), 734-739.
[http://dx.doi.org/10.1016/j.tips.2011.07.006] [PMID: 21880378]
[10]
Graus-Nunes, F.; Souza-Mello, V. The renin-angiotensin system as a target to solve the riddle of endocrine pancreas homeostasis. Biomed. Pharmacother., 2019, 109, 639-645.
[http://dx.doi.org/10.1016/j.biopha.2018.10.191] [PMID: 30404071]
[11]
Feng, P.; Wu, Z.; Liu, H.; Shen, Y.; Yao, X.; Li, X.; Shen, Z. Electroacupuncture improved chronic cerebral hypoperfusion-induced anxiety-like behavior and memory impairments in spontaneously hypertensive rats by downregulating the ACE/Ang II/AT1R Axis and upregulating the ACE2/Ang-(1-7)/MasR Axis. Neural Plast., 2020, 2020, 1-12.
[http://dx.doi.org/10.1155/2020/9076042] [PMID: 32184813]
[12]
Ali, Q.; Dhande, I.; Samuel, P.; Hussain, T. Angiotensin type 2 receptor null mice express reduced levels of renal angiotensin II type 2 receptor/angiotensin (1-7)/Mas receptor and exhibit greater high-fat diet-induced kidney injury. J. Renin Angiotensin Aldosterone Syst., 2016, 17(3), 17.
[http://dx.doi.org/10.1177/1470320316661871] [PMID: 27496559]
[13]
Tiwari, P; Tiwari, V; Gupta, S; Shukla, S; Hanif, K Activation of angiotensin-converting enzyme 2 protects against lipopolysaccharide-induced glial activation by modulating angiotensin-converting enzyme 2/angiotensin (1-7)/Mas Receptor Axis. Mol. Neurobiol., 2023, 60(1), 203-227.
[14]
Shoemaker, R.; AlSiraj, Y.; Chen, J.; Cassis, L.A. Pancreatic AT1aR deficiency decreases insulin secretion in Obese C57BL/6 Mice. Am. J. Hypertens., 2019, 32(6), 597-604.
[http://dx.doi.org/10.1093/ajh/hpz042] [PMID: 30903169]
[15]
Leung, K.K.; Leung, P.S. Effects of hyperglycemia on angiotensin II receptor type 1 expression and insulin secretion in an INS-1E pancreatic beta-cell line. JOP, 2008, 9(3), 290-299.
[PMID: 18469441]
[16]
McMurray, J.J.; Holman, R.R.; Haffner, S.M.; Bethel, M.A.; Holzhauer, B.; Hua, T.A.; Belenkov, Y.; Boolell, M.; Buse, J.B.; Buckley, B.M.; Chacra, A.R.; Chiang, F.T.; Charbonnel, B.; Chow, C.C.; Davies, M.J.; Deedwania, P.; Diem, P.; Einhorn, D.; Fonseca, V.; Fulcher, G.R.; Gaciong, Z.; Gaztambide, S.; Giles, T.; Horton, E.; Ilkova, H.; Jenssen, T.; Kahn, S.E.; Krum, H.; Laakso, M.; Leiter, L.A.; Levitt, N.S.; Mareev, V.; Martinez, F.; Masson, C.; Mazzone, T.; Meaney, E.; Nesto, R.; Pan, C.; Prager, R.; Raptis, S.A.; Rutten, G.E.; Sandstroem, H.; Schaper, F.; Scheen, A.; Schmitz, O.; Sinay, I.; Soska, V.; Stender, S.; Tamás, G.; Tognoni, G.; Tuomilehto, J.; Villamil, A.S.; Vozár, J.; Califf, R.M. Effect of valsartan on the incidence of diabetes and cardiovascular events. N. Engl. J. Med., 2010, 362(16), 1477-1490.
[http://dx.doi.org/10.1056/NEJMoa1001121] [PMID: 20228403]
[17]
Li, J.; Zhu, R.; Liu, Y.; Yang, J.; Wang, X.; Geng, L.; Xu, T.; He, J. Angiotensin-(1-7) improves islet function in a rat model of streptozotocin- induced diabetes mellitus by up-regulating the expression of Pdx1/Glut2. Endocr. Metab. Immune Disord. Drug Targets, 2021, 21(1), 156-162.
[http://dx.doi.org/10.2174/1871530320666200717161538] [PMID: 32679026]
[18]
Bartel, D.P. MicroRNAs. Cell, 2004, 116(2), 281-297.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[19]
Guay, C.; Roggli, E.; Nesca, V.; Jacovetti, C.; Regazzi, R. Diabetes mellitus, a microRNA-related disease? Transl. Res., 2011, 157(4), 253-264.
[http://dx.doi.org/10.1016/j.trsl.2011.01.009] [PMID: 21420036]
[20]
Zhang, A.; Li, D.; Liu, Y.; Li, J.; Zhang, Y.; Zhang, C.Y. Islet β cell: An endocrine cell secreting miRNAs. Biochem. Biophys. Res. Commun., 2018, 495(2), 1648-1654.
[http://dx.doi.org/10.1016/j.bbrc.2017.12.028] [PMID: 29223394]
[21]
Ding, Y.; Zhong, J.; Wang, Y.; Xie, W. Proteomic and microRNA omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation. Exp. Ther. Med., 2020, 21(2), 122.
[http://dx.doi.org/10.3892/etm.2020.9554] [PMID: 33335585]
[22]
van de Bunt, M.; Gaulton, K.J.; Parts, L.; Moran, I.; Johnson, P.R.; Lindgren, C.M.; Ferrer, J.; Gloyn, A.L.; McCarthy, M.I. The miRNA pro-file of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis. PLoS One, 2013, 8(1), e55272.
[http://dx.doi.org/10.1371/journal.pone.0055272] [PMID: 23372846]
[23]
Eliasson, L.; Esguerra, J.L.S. MicroRNA networks in pancreatic islet cells: Normal function and type 2 diabetes. Diabetes, 2020, 69(5), 804-812.
[http://dx.doi.org/10.2337/dbi19-0016] [PMID: 32312896]
[24]
Obama, T.; Eguchi, S. MicroRNA as a novel component of the tissue renin angiotensin system. J. Mol. Cell. Cardiol., 2014, 75, 98-99.
[http://dx.doi.org/10.1016/j.yjmcc.2014.07.004] [PMID: 25064430]
[25]
Arthurs, A.L.; Lumbers, E.R.; Pringle, K.G. MicroRNA mimics that target the placental renin–angiotensin system inhibit trophoblast proliferation. Mol. Hum. Reprod., 2019, 25(4), 218-227.
[http://dx.doi.org/10.1093/molehr/gaz010] [PMID: 30869150]
[26]
Hagiwara, S.; McClelland, A.; Kantharidis, P. MicroRNA in diabetic nephropathy: Renin angiotensin, aGE/RAGE, and oxidative stress pathway. J. Diabetes Res., 2013, 2013, 1-11.
[http://dx.doi.org/10.1155/2013/173783] [PMID: 24575418]
[27]
Wang, T.; Min, X.; Wang, T.; Cao, Y.; Liu, J.; Li, J. MicroRNAs: A novel promising therapeutic target for cerebral ischemia/reperfusion injury? Neural Regen. Res., 2015, 10(11), 1799-1808.
[http://dx.doi.org/10.4103/1673-5374.170302] [PMID: 26807114]
[28]
Poy, M.N.; Eliasson, L.; Krutzfeldt, J.; Kuwajima, S.; Ma, X.; MacDonald, P.E.; Pfeffer, S.; Tuschl, T.; Rajewsky, N.; Rorsman, P.; Stoffel, M. A pancreatic islet-specific microRNA regulates insulin secretion. Nature, 2004, 432(7014), 226-230.
[http://dx.doi.org/10.1038/nature03076] [PMID: 15538371]
[29]
Eliasson, L. The small RNA miR-375-a pancreatic islet abundant miRNA with multiple roles in endocrine beta cell function. Mol. Cell. Endocrinol., 2017, 456, 95-101.
[http://dx.doi.org/10.1016/j.mce.2017.02.043] [PMID: 28254488]
[30]
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]
[31]
Dumortier, O.; Fabris, G.; Pisani, D.F.; Casamento, V.; Gautier, N.; Hinault, C.; Lebrun, P.; Duranton, C.; Tauc, M.; Dalle, S.; Kerr-Conte, J.; Pattou, F.; Prentki, M.; Van Obberghen, E. microRNA-375 regulates glucose metabolism-related signaling for insulin secretion. J. Endocrinol., 2020, 244(1), 189-200.
[http://dx.doi.org/10.1530/JOE-19-0180] [PMID: 31697642]
[32]
Hu, S.; Zhang, M.; Sun, F.; Ren, L.; He, X.; Hua, J.; Peng, S. miR-375 controls porcine pancreatic stem cell fate by targeting 3-phosphoinositide-dependent protein kinase-1 (Pdk1). Cell Prolif., 2016, 49(3), 395-406.
[http://dx.doi.org/10.1111/cpr.12263] [PMID: 27218665]
[33]
Chen, Z.; Liu, H.; Yang, H.; Gao, Y.; Zhang, G.; Hu, J. The long noncoding RNA, TINCR, functions as a competing endogenous RNA to regu-late PDK1 expression by sponging miR-375 in gastric cancer. OncoTargets Ther., 2017, 10, 3353-3362.
[http://dx.doi.org/10.2147/OTT.S137726] [PMID: 28744139]
[34]
Jia-yuan, X.; Wei, S.; Fang-fang, L.; Zhi-jian, D.; Long-he, C.; Sen, L. Corrigendum to “miR-375 inhibits the proliferation and invasion of nasopharyngeal carcinoma cells by suppressing PDK1”. BioMed Res. Int., 2020, 2020, 1-2.
[http://dx.doi.org/10.1155/2020/3595402] [PMID: 32280708]
[35]
Wang, J.; Sun, X. MicroRNA-375 inhibits the proliferation, migration and invasion of kidney cancer cells by triggering apoptosis and modulation of PDK1 expression. Environ. Toxicol. Pharmacol., 2018, 62, 227-233.
[http://dx.doi.org/10.1016/j.etap.2018.08.002] [PMID: 30098579]
[36]
El Ouaamari, A.; Baroukh, N.; Martens, G.A.; Lebrun, P.; Pipeleers, D.; van Obberghen, E. miR-375 targets 3′-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic β-cells. Diabetes, 2008, 57(10), 2708-2717.
[http://dx.doi.org/10.2337/db07-1614] [PMID: 18591395]
[37]
Li, Y.; Xu, X.; Liang, Y.; Liu, S.; Xiao, H.; Li, F.; Cheng, H.; Fu, Z. miR-375 enhances palmitate-induced lipoapoptosis in insulin-secreting NIT-1 cells by repressing myotrophin (V1) protein expression. Int. J. Clin. Exp. Pathol., 2010, 3(3), 254-264.
[PMID: 20224724]
[38]
Miyazaki, J.I.; Araki, K.; Yamato, E.; Ikegami, H.; Asano, T.; Shibasaki, Y.; Oka, Y.; Yamamura, K.I. Establishment of a pancreatic beta cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms. Endocrinology, 1990, 127(1), 126-132.
[http://dx.doi.org/10.1210/endo-127-1-126] [PMID: 2163307]
[39]
Nakashima, K.; Kanda, Y.; Hirokawa, Y.; Kawasaki, F.; Matsuki, M.; Kaku, K. MIN6 is not a pure beta cell line but a mixed cell line with other pancreatic endocrine hormones. Endocr. J., 2009, 56(1), 45-53.
[http://dx.doi.org/10.1507/endocrj.K08E-172] [PMID: 18845907]
[40]
Kovalski, J.R.; Bhaduri, A.; Zehnder, A.M.; Neela, P.H.; Che, Y.; Wozniak, G.G.; Khavari, P.A. The functional proximal proteome of oncogenic ras includes mTORC2. Mol. Cell, 2019, 73(4), 830-844.e12.
[http://dx.doi.org/10.1016/j.molcel.2018.12.001] [PMID: 30639242]
[41]
Yuan, T.; Lupse, B.; Maedler, K.; Ardestani, A. mTORC2 Signaling: A path for pancreatic β Cell’s growth and function. J. Mol. Biol., 2018, 430(7), 904-918.
[http://dx.doi.org/10.1016/j.jmb.2018.02.013] [PMID: 29481838]
[42]
Kemp, J.R.; Unal, H.; Desnoyer, R.; Yue, H.; Bhatnagar, A.; Karnik, S.S. Angiotensin II-regulated microRNA 483-3p directly targets multiple components of the renin–angiotensin system. J. Mol. Cell. Cardiol., 2014, 75, 25-39.
[http://dx.doi.org/10.1016/j.yjmcc.2014.06.008] [PMID: 24976017]
[43]
Yang, M.; Song, J.J.; Yang, X.C.; Zhong, G.Z.; Zhong, J.C. MiRNA-122-5p inhibitor abolishes angiotensin II–mediated loss of autophagy and promotion of apoptosis in rat cardiofibroblasts by modulation of the apelin-AMPK-mTOR signaling. In Vitro Cell. Dev. Biol. Anim., 2022, 58(2), 136-148.
[http://dx.doi.org/10.1007/s11626-022-00651-4] [PMID: 35133561]
[44]
Arthurs, A.L.; Lumbers, E.R.; Delforce, S.J.; Mathe, A.; Morris, B.J.; Pringle, K.G. The role of oxygen in regulating microRNAs in control of the placental renin–angiotensin system. Mol. Hum. Reprod., 2019, 25(4), 206-217.
[http://dx.doi.org/10.1093/molehr/gaz004] [PMID: 30726964]
[45]
Wu, W.H.; Hu, C.P.; Chen, X.P.; Zhang, W.F.; Li, X.W.; Xiong, X.M.; Li, Y.J. MicroRNA-130a mediates proliferation of vascular smooth muscle cells in hypertension. Am. J. Hypertens., 2011, 24(10), 1087-1093.
[http://dx.doi.org/10.1038/ajh.2011.116] [PMID: 21753805]
[46]
Luo, P.; Zhang, W.F.; Qian, Z.X.; Xiao, L.F.; Wang, H.; Zhu, T.T.; Li, F.; Hu, C.P.; Zhang, Z. MiR-590-5p-meidated LOX-1 upregulation promotes Angiotensin II-induced endothelial cell apoptosis. Biochem. Biophys. Res. Commun., 2016, 471(4), 402-408.
[http://dx.doi.org/10.1016/j.bbrc.2016.02.074] [PMID: 26906623]
[47]
Feng, H.; Wu, J.; Chen, P.; Wang, J.; Deng, Y.; Zhu, G.; Xian, J.; Huang, L.; Ouyang, W. MicroRNA‐375‐3p inhibitor suppresses angiotensin II‐induced cardiomyocyte hypertrophy by promoting lactate dehydrogenase B expression. J. Cell. Physiol., 2019, 234(8), 14198-14209.
[http://dx.doi.org/10.1002/jcp.28116] [PMID: 30618075]
[48]
Nathan, G.; Kredo-Russo, S.; Geiger, T.; Lenz, A.; Kaspi, H.; Hornstein, E.; Efrat, S. MiR-375 promotes redifferentiation of adult human β cells expanded in vitro. PLoS One, 2015, 10(4), e0122108.
[http://dx.doi.org/10.1371/journal.pone.0122108] [PMID: 25875172]
[49]
Gezginci-Oktayoglu, S.; Sancar, S.; Karatug-Kacar, A.; Bolkent, S. miR‐375 induces adipogenesis through targeting Erk1 in pancreatic duct cells under the influence of sodium palmitate. J. Cell. Physiol., 2021, 236(5), 3881-3895.
[http://dx.doi.org/10.1002/jcp.30129] [PMID: 33107061]
[50]
Li, C.; Chen, L.; Zhao, Y.; Chen, S.; Fu, L.; Jiang, Y.; Gao, S.; Liu, Z.; Wang, F.; Zhu, X.; Rao, J.; Zhang, J.; Zhou, X. Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model. Gene, 2017, 598, 20-26.
[http://dx.doi.org/10.1016/j.gene.2016.10.033] [PMID: 27777110]
[51]
Wei, R.; Yang, J.; Liu, G.; Gao, M.; Hou, W.; Zhang, L.; Gao, H.; Liu, Y.; Chen, G.; Hong, T. Dynamic expression of microRNAs during the differentiation of human embryonic stem cells into insulin-producing cells. Gene, 2013, 518(2), 246-255.
[http://dx.doi.org/10.1016/j.gene.2013.01.038] [PMID: 23370336]
[52]
Poy, M.N.; Hausser, J.; Trajkovski, M.; Braun, M.; Collins, S.; Rorsman, P.; Zavolan, M.; Stoffel, M. miR-375 maintains normal pancreatic α- and β-cell mass. Proc. Natl. Acad. Sci., 2009, 106(14), 5813-5818.
[http://dx.doi.org/10.1073/pnas.0810550106] [PMID: 19289822]
[53]
Pudewell, S.; Lissy, J.; Nakhaeizadeh, H.; Mosaddeghzadeh, N.; Nakhaei-Rad, S.; Dvorsky, R.; Ahmadian, M.R. New mechanistic insights into the RAS-SIN1 interaction at the membrane. Front. Cell Dev. Biol., 2022, 10, 987754.
[http://dx.doi.org/10.3389/fcell.2022.987754] [PMID: 36274845]
[54]
Jacinto, E.; Facchinetti, V.; Liu, D.; Soto, N.; Wei, S.; Jung, S.Y.; Huang, Q.; Qin, J.; Su, B. SIN1/MIP1 maintains rictor-mTOR complex integ-rity and regulates Akt phosphorylation and substrate specificity. Cell, 2006, 127(1), 125-137.
[http://dx.doi.org/10.1016/j.cell.2006.08.033] [PMID: 16962653]
[55]
Frias, M.A.; Thoreen, C.C.; Jaffe, J.D.; Schroder, W.; Sculley, T.; Carr, S.A.; Sabatini, D.M. mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr. Biol., 2006, 16(18), 1865-1870.
[http://dx.doi.org/10.1016/j.cub.2006.08.001] [PMID: 16919458]
[56]
Yang, Q.; Inoki, K.; Ikenoue, T.; Guan, K.L. Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev., 2006, 20(20), 2820-2832.
[http://dx.doi.org/10.1101/gad.1461206] [PMID: 17043309]
[57]
Moraitis, D.; Karanikou, M.; Liakou, C.; Dimas, K.; Tzimas, G. SIN1, a critical component of the mTOR-Rictor complex, is overexpressed and associated with AKT activation in medullary and aggressive papillary thyroid carcinomas. Surgery, 2014, 156(6), 1542-1548.
[http://dx.doi.org/10.1016/j.surg.2014.08.095]
[58]
Facchinetti, V.; Ouyang, W.; Wei, H.; Soto, N.; Lazorchak, A.; Gould, C.; Lowry, C.; Newton, A.C.; Mao, Y.; Miao, R.Q.; Sessa, W.C.; Qin, J.; Zhang, P.; Su, B.; Jacinto, E. The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO J., 2008, 27(14), 1932-1943.
[http://dx.doi.org/10.1038/emboj.2008.120] [PMID: 18566586]
[59]
García-Martínez, J.M.; Alessi, D.R. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem. J., 2008, 416(3), 375-385.
[http://dx.doi.org/10.1042/BJ20081668] [PMID: 18925875]
[60]
Kim, S.G.; Sung, J.Y.; Kim, J.R.; Choi, H.C. Fisetin-induced PTEN expression reverses cellular senescence by inhibiting the mTORC2-Akt Ser473 phosphorylation pathway in vascular smooth muscle cells. Exp. Gerontol., 2021, 156, 111598.
[http://dx.doi.org/10.1016/j.exger.2021.111598] [PMID: 34695518]
[61]
Wang, G.; Liu, M.; Wang, H.; Yu, S.; Jiang, Z.; Sun, J.; Han, K.; Shen, J.; Zhu, M.; Lin, Z.; Jiang, C.; Guo, M. Centrosomal protein of 55 regulates glucose metabolism, proliferation and apoptosis of glioma cells via the Akt/mTOR signaling pathway. J. Cancer, 2016, 7(11), 1431-1440.
[http://dx.doi.org/10.7150/jca.15497] [PMID: 27471559]
[62]
Somanath, P.R.; Razorenova, O.V.; Chen, J.; Byzova, T.V. Akt1 in endothelial cell and angiogenesis. Cell Cycle, 2006, 5(5), 512-518.
[http://dx.doi.org/10.4161/cc.5.5.2538] [PMID: 16552185]
[63]
Jara, M.A.; Werneck-De-Castro, J.P.; Lubaczeuski, C.; Johnson, J.D.; Bernal-Mizrachi, E. Pancreatic and duodenal homeobox-1 (PDX1) con-tributes to β-cell mass expansion and proliferation induced by Akt/PKB pathway. Islets, 2020, 12(2), 32-40.
[http://dx.doi.org/10.1080/19382014.2020.1762471] [PMID: 32876522]
[64]
da Costa, R.M.; Neves, K.B.; Mestriner, F.L.; Louzada-Junior, P.; Bruder-Nascimento, T.; Tostes, R.C. TNF-α induces vascular insulin re-sistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice. Cardiovasc. Diabetol., 2016, 15(1), 119.
[http://dx.doi.org/10.1186/s12933-016-0443-0] [PMID: 27562094]
[65]
Ždychová, J.; Komers, R. Emerging role of Akt kinase/protein kinase B signaling in pathophysiology of diabetes and its complications. Physiol. Res., 2005, 54(1), 1-16.
[http://dx.doi.org/10.33549/physiolres.930582] [PMID: 15717836]
[66]
Šrámek, J.; Němcová-Fürstová, V.; Kovář, J. Kinase signaling in apoptosis induced by saturated fatty acids in pancreatic β-cells. Int. J. Mol. Sci., 2016, 17(9), 1400.
[http://dx.doi.org/10.3390/ijms17091400] [PMID: 27626409]
[67]
Yao, S.; Zhang, J.; Zhan, Y.; Shi, Y.; Yu, Y.; Zheng, L.; Xu, N.; Luo, G. Insulin resistance in apolipoprotein m knockout mice is mediated by the protein kinase Akt signaling pathway. Endocr. Metab. Immune Disord. Drug Targets, 2020, 20(5), 771-780.
[http://dx.doi.org/10.2174/1871530319666191023125820] [PMID: 31702495]
[68]
Liu, H.; Zhang, D.; Zhou, Y.; Cui, S. MicroRNA-7a inhibits Isl1 expression to regulate insulin secretion by targeting Raf1 and Mapkap1 in NIT-1 cells. In Vitro Cell. Dev. Biol. Anim., 2021, 57(8), 817-824.
[http://dx.doi.org/10.1007/s11626-021-00611-4] [PMID: 34713362]
[69]
Mukaida, S.; Evans, B.A.; Bengtsson, T.; Hutchinson, D.S.; Sato, M. Adrenoceptors promote glucose uptake into adipocytes and muscle by an insulin-independent signaling pathway involving mechanistic target of rapamycin complex 2. Pharmacol. Res., 2017, 116, 87-92.
[http://dx.doi.org/10.1016/j.phrs.2016.12.022] [PMID: 28025104]
[70]
Yang, J.; Waldron, R.T.; Su, H.Y.; Moro, A.; Chang, H.H.; Eibl, G.; Ferreri, K.; Kandeel, F.R.; Lugea, A.; Li, L.; Pandol, S.J. Insulin promotes proliferation and fibrosing responses in activated pancreatic stellate cells. Am. J. Physiol. Gastrointest. Liver Physiol., 2016, 311(4), G675-G687.
[http://dx.doi.org/10.1152/ajpgi.00251.2016] [PMID: 27609771]

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