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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

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

Commentary

Searching for a Link between Bone Decay and Diabetes Type 2

Author(s): Ciro G. Isacco, Kieu C.D. Nguyen, Van H. Pham, Gianna Di Palma, Sergey K. Aityan, Diego Tomassone*, Pietro Distratis, Rita Lazzaro, Mario G. Balzanelli and Francesco Inchingolo

Volume 22, Issue 9, 2022

Published on: 24 March, 2022

Page: [904 - 910] Pages: 7

DOI: 10.2174/1871530322666220324150327

Abstract

The current commentary describes the possible existing link between metabolic diseases such as diabetes type 2 and the degenerative patterns of bones via the molecular mechanism that inhibits the mesenchymal stem cells’ differentiation into osteoblasts and osteocytes.

Keywords: Diabetes type 1-2, regenerative medicine, enteric nervous system (ENS), central nervous system (CNS), mesenchymal stem cells (MSCs), bone marrow (BM), osteoblasts, ageing, bone decay.

Graphical Abstract
[1]
Ramachandran, A.; Snehalatha, C.; Shetty, A.S.; Nanditha, A. Trends in prevalence of diabetes in Asian countries. World J. Diabetes, 2012, 3(6), 110-117.
[http://dx.doi.org/10.4239/wjd.v3.i6.110] [PMID: 22737281]
[2]
Wu, Y.; Ding, Y.; Tanaka, Y.; Zhang, W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int. J. Med. Sci., 2014, 11(11), 1185-1200.
[http://dx.doi.org/10.7150/ijms.10001] [PMID: 25249787]
[3]
Ahmed, A.S.I.; Sheng, M.H.; Wasnik, S.; Baylink, D.J.; Lau, K.W. Effect of aging on stem cells. World J. Exp. Med., 2017, 7(1), 1-10.
[http://dx.doi.org/10.5493/wjem.v7.i1.1] [PMID: 28261550]
[4]
Camihort, G.; Gómez Dumm, C.; Luna, G.; Ferese, C.; Jurado, S.; Moreno, G.; Spinedi, E.; Cónsole, G. Relationship between pituitary and adipose tissue after hypothalamic denervation in the female rat. A morphometric immunohistochemical study. Cells Tissues Organs, 2005, 179(4), 192-201.
[http://dx.doi.org/10.1159/000085954] [PMID: 16046865]
[5]
Halpern-Silveira, D.; Susin, L.R.; Borges, L.R.; Paiva, S.I.; Assunção, M.C.; Gonzalez, M.C. Body weight and fat-free mass changes in a cohort of patients receiving chemotherapy. Support. Care Cancer, 2010, 18(5), 617-625.
[http://dx.doi.org/10.1007/s00520-009-0703-6] [PMID: 19621246]
[6]
Halpern, A.; Mancini, M.C.; Magalhães, M.E.; Fisberg, M.; Radominski, R.; Bertolami, M.C.; Bertolami, A.; de Melo, M.E.; Zanella, M.T.; Queiroz, M.S.; Nery, M. Metabolic syndrome, dyslipidemia, hypertension and type 2 diabetes in youth: From diagnosis to treatment. Diabetol. Metab. Syndr., 2010, 2(1), 55.
[http://dx.doi.org/10.1186/1758-5996-2-55] [PMID: 20718958]
[7]
Neergaard, J.S.; Dragsbæk, K.; Christiansen, C.; Nielsen, H.B.; Brix, S.; Karsdal, M.A.; Henriksen, K. Metabolic syndrome, insulin resistance, and cognitive dysfunction: Does your metabolic profile affect your brain? Diabetes, 2017, 66(7), 1957-1963.
[http://dx.doi.org/10.2337/db16-1444] [PMID: 28389469]
[8]
Moreno-Indias, I.; Cardona, F.; Tinahones, F.J. Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus. Front. Microbiol., 2014, 5, 190.
[http://dx.doi.org/10.3389/fmicb.2014.00190]
[9]
Parekh, P.J.; Balart, L.A.; Johnson, D.A. The influence of the gut microbiome on obesity, metabolic syndrome and gastrointestinal disease. Clin. Transl. Gastroenterol., 2015, 6(6), e91.
[http://dx.doi.org/10.1038/ctg.2015.16] [PMID: 26087059]
[10]
Hur, K.Y.; Lee, M.S. Gut microbiota and metabolic disorders. Diabetes Metab. J., 2015, 39(3), 198-203.
[http://dx.doi.org/10.4093/dmj.2015.39.3.198] [PMID: 26124989]
[11]
Guarner, V.; Rubio-Ruiz, M.E. Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease. Interdiscip. Top. Gerontol., 2015, 40, 99-106.
[http://dx.doi.org/10.1159/000364934] [PMID: 25341516]
[12]
Gargiulo, C.; Pham, H.V.; Huynh, T.D.; Trieu, V.; Kieu, N.; Shiffman, M.; Holterman, M.; Aityan, S.; Filgueira, L. Novel therapeutic strategy in the treatment of diabetes type 2, the use of autologous peripheral blood stem cells in 15 patients: Is there any relation with the incretin-GLP-1/GIP Axis? Br. J. Med. Med. Res., 2017, 20(7), 1-16.
[http://dx.doi.org/10.9734/BJMMR/2017/32206]
[13]
DiPersio, J.F. Diabetic stem-cell “mobilopathy”. N. Engl. J. Med., 2011, 365(26), 2536-2538.
[http://dx.doi.org/10.1056/NEJMcibr1112347] [PMID: 22204729]
[14]
Seewoodhary, J.; Evans, P.J. Diabetes and stem cells: Endogenous effects and reparative mechanisms. Br. J. Diabetes Vasc. Dis., 2013, 13(5-6), 1-7.
[http://dx.doi.org/10.1177/1474651413502684]
[15]
Saito, H.; Yamamoto, Y.; Yamamoto, H. Diabetes alters subsets of endothelial progenitor cells that reside in blood, bone marrow, and spleen. Am. J. Physiol. Cell Physiol., 2012, 302(6), C892-C901.
[http://dx.doi.org/10.1152/ajpcell.00380.2011] [PMID: 22159079]
[16]
van der Flier, L.G.; Clevers, H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu. Rev. Physiol., 2009, 71(1), 241-260.
[http://dx.doi.org/10.1146/annurev.physiol.010908.163145] [PMID: 18808327]
[17]
Jarajapu, Y.P.R.; Grant, M.B. The promise of cell-based therapies for diabetic complications: Challenges and solutions. Circ. Res., 2010, 106(5), 854-869.
[http://dx.doi.org/10.1161/CIRCRESAHA.109.213140] [PMID: 20299675]
[18]
Tonelli, M.; Muntner, P.; Lloyd, A.; Manns, B.J.; Klarenbach, S.; Pannu, N.; James, M.T.; Hemmelgarn, B.R. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: A population-level cohort study. Lancet, 2012, 380(9844), 807-814.
[http://dx.doi.org/10.1016/S0140-6736(12)60572-8] [PMID: 22717317]
[19]
Festi, D.; Schiumerini, R.; Eusebi, L.H.; Marasco, G.; Taddia, M.; Colecchia, A. Gut microbiota and metabolic syndrome. World J. Gastroenterol., 2014, 20(43), 16079-16094.
[http://dx.doi.org/10.3748/wjg.v20.i43.16079] [PMID: 25473159]
[20]
Yin, F.; Banerjee, R.; Thomas, B.; Zhou, P.; Qian, L.; Jia, T.; Ma, X.; Ma, Y.; Iadecola, C.; Beal, M.F.; Nathan, C.; Ding, A. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J. Exp. Med., 2010, 207(1), 117-128.
[http://dx.doi.org/10.1084/jem.20091568] [PMID: 20026663]
[21]
Boyce, B.F.; Xing, L. The RANKL/RANK/OPG pathway. Curr. Osteoporos. Rep., 2007, 5(3), 98-104.
[http://dx.doi.org/10.1007/s11914-007-0024-y] [PMID: 17925190]
[22]
Park, J.H.; Lee, N.K.; Lee, S.Y. Current understanding of RANK signaling in osteoclast differentiation and maturation. Mol. Cells, 2017, 40(10), 706-713.
[PMID: 29047262]
[23]
Arango Duque, G.; Descoteaux, A. Macrophage cytokines: Involvement in immunity and infectious diseases. Front. Immunol., 2014, 5, 491.
[http://dx.doi.org/10.3389/fimmu.2014.00491] [PMID: 25339958]
[24]
Gianatti, E.J.; Grossmann, M. Testosterone deficiency in men with Type 2 diabetes: Pathophysiology and treatment. Diabet. Med., 2020, 37(2), 174-186.
[http://dx.doi.org/10.1111/dme.13977] [PMID: 31006133]
[25]
Li, S.Y.; Zhao, Y.L.; Yang, Y.F.; Wang, X.; Nie, M.; Wu, X.Y.; Mao, J.F.; Veglio, F. Metabolic effects of testosterone replacement therapy in patients with type 2 diabetes mellitus or metabolic syndrome: A meta-analysis. Int. J. Endocrinol., 2020, 2020, 4732021.
[http://dx.doi.org/10.1155/2020/4732021] [PMID: 33061966]
[26]
Walsh, M.C.; Choi, Y. Biology of the RANKL-RANK-OPG system in immunity, bone, and beyond. Front. Immunol., 2014, 5, 511.
[http://dx.doi.org/10.3389/fimmu.2014.00511] [PMID: 25368616]
[27]
Ghanim, H.; Dhindsa, S.; Green, K.; Abuaysheh, S.; Batra, M.; Makdissi, A.; Chaudhuri, A.; Dandona, P. Increase in osteocalcin following testosterone therapy in men with type 2 diabetes and subnormal free testosterone. J. Endocr. Soc., 2019, 3(8), 1617-1630.
[http://dx.doi.org/10.1210/js.2018-00426] [PMID: 31403089]
[28]
Galibert, L; Tometsko, ME; Anderson, DM The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of NF-kappaB, a member of the TNFR superfamily. J. Biol. Chem., 1998, 273(51), 34120-7.10.
[29]
Collins, K.H.; Paul, H.A.; Reimer, R.A.; Seerattan, R.A.; Hart, D.A.; Herzog, W. Relationship between inflammation, the gut microbiota, and metabolic osteoarthritis development: Studies in a rat model. Osteoarthritis Cartilage, 2015, 23(11), 1989-1998.
[http://dx.doi.org/10.1016/j.joca.2015.03.014] [PMID: 26521745]
[30]
Cristofori, F.; Dargenio, V.N.; Dargenio, C.; Miniello, V.L.; Barone, M.; Francavilla, R. Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: A door to the body. Front. Immunol., 2021, 12, 578386.
[http://dx.doi.org/10.3389/fimmu.2021.578386] [PMID: 33717063]
[31]
Huang, J.; Tan, Q.; Tai, N.; Pearson, J.A.; Li, Y.; Chao, C.; Zhang, L.; Peng, J.; Xing, Y.; Zhang, L.; Hu, Y.; Zhou, Z.; Wong, F.S.; Wen, L. IL-10 deficiency accelerates type 1 diabetes development via modulation of innate and adaptive immune cells and gut microbiota in BDC2.5 NOD mice. Front. Immunol., 2021, 12, 702955.
[http://dx.doi.org/10.3389/fimmu.2021.702955] [PMID: 34394099]
[32]
Walsh, M.C.; Kim, N.; Kadono, Y. Osteoimmunology: Interplay between the immune system and bone metabolism. Annu. Rev. Immunol., 2006, 24, 33-63.
[http://dx.doi.org/10.1146/annurev.immunol.24.021605.090646]
[33]
Flore, R.; Ponziani, F.R.; Di Rienzo, T.A.; Zocco, M.A.; Flex, A.; Gerardino, L.; Lupascu, A.; Santoro, L.; Santoliquido, A.; Di Stasio, E.; Chierici, E.; Lanti, A.; Tondi, P.; Gasbarrini, A. Something more to say about calcium homeostasis: The role of vitamin K2 in vascular calcification and osteoporosis. Eur. Rev. Med. Pharmacol. Sci., 2013, 17(18), 2433-2440.
[PMID: 24089220]
[34]
Iwamoto, J.; Takeda, T.; Sato, Y. Interventions to prevent bone loss in astronauts during space flight. Keio J. Med., 2005, 54(2), 55-59.
[http://dx.doi.org/10.2302/kjm.54.55] [PMID: 16077253]
[35]
Shearer, M.J.; Newman, P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J. Lipid Res., 2014, 55(3), 345-362.
[http://dx.doi.org/10.1194/jlr.R045559] [PMID: 24489112]
[36]
Fusaro, M.; Mereu, M.C.; Aghi, A.; Iervasi, G.; Gallieni, M. Vitamin K and bone. Clin. Cases Miner. Bone Metab., 2017, 14(2), 200-206.
[http://dx.doi.org/10.11138/ccmbm/2017.14.1.200] [PMID: 29263734]
[37]
Danziger, J. Vitamin K-dependent proteins, warfarin, and vascular calcification. Clin. J. Am. Soc. Nephrol., 2008, 3(5), 1504-1510.
[http://dx.doi.org/10.2215/CJN.00770208] [PMID: 18495950]
[38]
Price, P.A.; Faus, S.A.; Williamson, M.K. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler. Thromb. Vasc. Biol., 1998, 18(9), 1400-1407.
[http://dx.doi.org/10.1161/01.ATV.18.9.1400] [PMID: 9743228]
[39]
Violi, F.; Lip, G.Y.H.; Pignatelli, P.; Pastori, D. Interaction between dietary vitamin k intake and anticoagulation by vitamin K antagonists: Is it really true?: A systematic review. Medicine (Baltimore), 2016, 95(10), e2895.
[http://dx.doi.org/10.1097/MD.0000000000002895] [PMID: 26962786]
[40]
Gröber, U.; Reichrath, J.; Holick, M.F.; Kisters, K.; Vitamin, K. An old vitamin in a new perspective. Dermatoendocrinol, 2015, 6(1), e968490.
[http://dx.doi.org/10.4161/19381972.2014.968490] [PMID: 26413183]
[41]
Oldenburg, J.; Bevans, C.G.; Müller, C.R.; Watzka, M. Vitamin K epoxide reductase complex subunit 1 (VKORC1): The key protein of the vitamin K cycle. Antioxid. Redox Signal., 2006, 8(3-4), 347-353.
[http://dx.doi.org/10.1089/ars.2006.8.347] [PMID: 16677080]
[42]
Spohn, G.; Kleinridders, A.; Wunderlich, F.T.; Watzka, M.; Zaucke, F.; Blumbach, K.; Geisen, C.; Seifried, E.; Müller, C.; Paulsson, M.; Brüning, J.C.; Oldenburg, J. VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. Thromb. Haemost., 2009, 101(6), 1044-1050.
[http://dx.doi.org/10.1160/TH09-03-0204] [PMID: 19492146]
[43]
Igarashi, M.; Yogiashi, Y.; Mihara, M.; Takada, I.; Kitagawa, H.; Kato, S. Retraction for Igarashi et al., Vitamin K induces osteoblast differentiation through pregnane X receptor-mediated transcriptional control of the Msx2 gene. Mol. Cell. Biol., 2014, 34(5), 918.
[http://dx.doi.org/10.1128/MCB.00020-14] [PMID: 24509263]
[44]
Blair, H.C.; Larrouture, Q.C.; Li, Y.; Lin, H.; Beer-Stoltz, D.; Liu, L.; Tuan, R.S.; Robinson, L.J.; Schlesinger, P.H.; Nelson, D.J. Osteoblast differentiation and bone matrix formation in vivo and in vitro. Tissue Eng. Part B Rev., 2017, 23(3), 268-280.
[http://dx.doi.org/10.1089/ten.teb.2016.0454] [PMID: 27846781]
[45]
Yamaguchi, M.; Ma, Z.J. Inhibitory effect of menaquinone-7 (vitamin K2) on osteoclast-like cell formation and osteoclastic bone resorption in rat bone tissues in vitro. Mol. Cell. Biochem., 2001, 228(1-2), 39-47.
[http://dx.doi.org/10.1023/A:1013360308946] [PMID: 11855740]
[46]
Kim, M.; Na, W.; Sohn, C. Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice. J. Clin. Biochem. Nutr., 2013, 53(2), 108-113.
[http://dx.doi.org/10.3164/jcbn.13-25] [PMID: 24062608]
[47]
Yamauchi, M.; Yamaguchi, T.; Nawata, K.; Takaoka, S.; Sugimoto, T. Relationships between undercarboxylated osteocalcin and vitamin K intakes, bone turnover, and bone mineral density in healthy women. Clin. Nutr., 2010, 29(6), 761-765.
[http://dx.doi.org/10.1016/j.clnu.2010.02.010] [PMID: 20332058]
[48]
Yamaguchi, M. Role of nutritional factor menaquinone-7 in bone homeostasis and osteoporosis prevention. Integr. Mol. Med., 2014, 1(1), 1-6.
[http://dx.doi.org/10.15761/IMM.1000101]
[49]
Wu, W.J.; Kim, M.S.; Ahn, B.Y. The inhibitory effect of vitamin K on RANKL-induced osteoclast differentiation and bone resorption. Food Funct., 2015, 6(10), 3351-3358.
[http://dx.doi.org/10.1039/C5FO00544B] [PMID: 26267519]
[50]
Taylor, P.M. Role of amino acid transporters in amino acid sensing. Am. J. Clin. Nutr., 2014, 99(1), 223S-230S.
[http://dx.doi.org/10.3945/ajcn.113.070086] [PMID: 24284439]
[51]
Jewell, J.L.; Russell, R.C.; Guan, K.L. Amino acid signalling upstream of mTOR. Nat. Rev. Mol. Cell Biol., 2013, 14(3), 133-139.
[http://dx.doi.org/10.1038/nrm3522] [PMID: 23361334]
[52]
Jia, G.; Aroor, A.R.; Martinez-Lemus, L.A.; Sowers, J.R. Overnutrition, mTOR signaling, and cardiovascular diseases. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2014, 307(10), R1198-R1206.
[http://dx.doi.org/10.1152/ajpregu.00262.2014] [PMID: 25253086]
[53]
Passtoors, W.M.; Beekman, M.; Deelen, J.; van der Breggen, R.; Maier, A.B.; Guigas, B.; Derhovanessian, E.; van Heemst, D.; de Craen, A.J.; Gunn, D.A.; Pawelec, G.; Slagboom, P.E. Gene expression analysis of mTOR pathway: Association with human longevity. Aging Cell, 2013, 12(1), 24-31.
[http://dx.doi.org/10.1111/acel.12015] [PMID: 23061800]
[54]
Engelman, J.A.; Luo, J.; Cantley, L.C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet., 2006, 7(8), 606-619.
[http://dx.doi.org/10.1038/nrg1879] [PMID: 16847462]
[55]
Chalhoub, N.; Baker, S.J. PTEN and the PI3-kinase pathway in cancer. Annu. Rev. Pathol., 2009, 4(1), 127-150.
[http://dx.doi.org/10.1146/annurev.pathol.4.110807.092311] [PMID: 18767981]
[56]
Um, S.H.; Frigerio, F.; Watanabe, M.; Picard, F.; Joaquin, M.; Sticker, M.; Fumagalli, S.; Allegrini, P.R.; Kozma, S.C.; Auwerx, J.; Thomas, G. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature, 2004, 431(7005), 200-205.
[http://dx.doi.org/10.1038/nature02866] [PMID: 15306821]
[57]
Thedieck, K.; Holzwarth, B.; Prentzell, M.T.; Boehlke, C.; Kläsener, K.; Ruf, S.; Sonntag, A.G.; Maerz, L.; Grellscheid, S.N.; Kremmer, E.; Nitschke, R.; Kuehn, E.W.; Jonker, J.W.; Groen, A.K.; Reth, M.; Hall, M.N.; Baumeister, R. Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells. Cell, 2013, 154(4), 859-874.
[http://dx.doi.org/10.1016/j.cell.2013.07.031] [PMID: 23953116]
[58]
Melnik, B.C.; John, S.M.; Carrera-Bastos, P.; Cordain, L. The impact of cow’s milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer. Nutr. Metab. (Lond.), 2012, 9(1), 74.
[http://dx.doi.org/10.1186/1743-7075-9-74] [PMID: 22891897]
[59]
Uno, K.; Yamada, T.; Ishigaki, Y.; Imai, J.; Hasegawa, Y.; Sawada, S.; Kaneko, K.; Ono, H.; Asano, T.; Oka, Y.; Katagiri, H. A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals. Nat. Commun., 2015, 6(1), 7940.
[http://dx.doi.org/10.1038/ncomms8940] [PMID: 26268630]
[60]
Ali, M.; Bukhari, S.A.; Ali, M.; Lee, H.W. Upstream signalling of mTORC1 and its hyperactivation in type 2 diabetes (T2D). BMB Rep., 2017, 50(12), 601-609.
[http://dx.doi.org/10.5483/BMBRep.2017.50.12.206] [PMID: 29187279]
[61]
Martelli, A.M.; Buontempo, F. McCubrey, JA Drug discovery targeting mTor pathway. Clin. Sci., 2018, 132(5), 543-568.
[http://dx.doi.org/10.1042/CS20171158]
[62]
Jiang, M.; Fu, X.; Yang, H.; Long, F.; Chen, J. mTORC1 signaling promotes limb bud cell growth and chondrogenesis. J. Cell. Biochem., 2017, 118(4), 748-753.
[http://dx.doi.org/10.1002/jcb.25728] [PMID: 27606668]
[63]
Xu, G.; Li, Z.; Ding, L.; Tang, H.; Guo, S.; Liang, H.; Wang, H.; Zhang, W. Intestinal mTOR regulates GLP-1 production in mouse L cells. Diabetologia, 2015, 58(8), 1887-1897.
[http://dx.doi.org/10.1007/s00125-015-3632-6] [PMID: 26037201]
[64]
Chen, J.; Tu, X.; Esen, E.; Joeng, K.S.; Lin, C.; Arbeit, J.M.; Rüegg, M.A.; Hall, M.N.; Ma, L.; Long, F. WNT7B promotes bone formation in part through mTORC1. PLoS Genet., 2014, 10(1), e1004145.
[http://dx.doi.org/10.1371/journal.pgen.1004145] [PMID: 24497849]
[65]
Karner, C.M.; Esen, E.; Okunade, A.L.; Patterson, B.W.; Long, F. Increased glutamine catabolism mediates bone anabolism in response to WNT signaling. J. Clin. Invest., 2015, 125(2), 551-562.
[http://dx.doi.org/10.1172/JCI78470] [PMID: 25562323]
[66]
Lim, J.; Shi, Y.; Karner, C.M.; Lee, S.Y.; Lee, W.C.; He, G.; Long, F. Dual function of Bmpr1a signaling in restricting preosteoblast proliferation and stimulating osteoblast activity in mouse. Development, 2016, 143(2), 339-347.
[PMID: 26657771]
[67]
Wu, Y.; Chhipa, R.R.; Cheng, J.; Zhang, H.; Mohler, J.L.; Ip, C. Androgen receptor-mTOR crosstalk is regulated by testosterone availability: Implication for prostate cancer cell survival. Anticancer Res., 2010, 30(10), 3895-3901.
[PMID: 21036700]
[68]
Ayada, C.; Toru, Ü.; Korkut, Y. Nesfatin-1 and its effects on different systems. Hippokratia, 2015, 19(1), 4-10.
[PMID: 26435639]
[69]
Kojima, M.; Kangawa, K. Ghrelin: Structure and function. Physiol. Rev., 2005, 85(2), 495-522.
[http://dx.doi.org/10.1152/physrev.00012.2004] [PMID: 15788704]
[70]
Wright, E.J.; Farrell, K.A.; Malik, N.; Kassem, M.; Lewis, A.L.; Wallrapp, C.; Holt, C.M. Encapsulated glucagon-like peptide-1-producing mesenchymal stem cells have a beneficial effect on failing pig hearts. Stem Cells Transl. Med., 2012, 1(10), 759-769.
[http://dx.doi.org/10.5966/sctm.2012-0064] [PMID: 23197668]

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