Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2017, Article ID 7680576, 9 pages
https://doi.org/10.1155/2017/7680576
Review Article

Serotonin and Its Receptor as a New Antioxidant Therapeutic Target for Diabetic Kidney Disease

1Department of Endocrinology, Metabolism, and Genetics, Jiangxi Provincial Children’s Hospital, Nanchang, Jiangxi, China
2Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, USA
3Department of Cardiovascular Disorders, The First Hospital of Jilin University, Changchun, China
4Department of Cardiovascular Disorders, Jiangxi Provincial Children’s Hospital, Nanchang, Jiangxi, China

Correspondence should be addressed to Yu Yang; moc.liamg@yexjhhyy

Received 2 May 2017; Accepted 13 July 2017; Published 8 August 2017

Academic Editor: Robertina Giacconi

Copyright © 2017 Yu Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. I. H. de Boer, T. C. Rue, Y. N. Hall, P. J. Heagerty, N. S. Weiss, and J. Himmelfarb, “Temporal trends in the prevalence of diabetic kidney disease in the United States,” The Journal of the American Medical Association, vol. 305, pp. 2532–2539, 2011. View at Google Scholar
  2. S. P. Silveiro, G. N. Araujo, M. N. Ferreira, F. D. Souza, H. M. Yamaguchi, and E. G. Camargo, “Chronic kidney disease epidemiology collaboration (ckd-epi) equation pronouncedly underestimates glomerular filtration rate in type 2 diabetes,” Diabetes Care, vol. 34, pp. 2353–2355, 2011. View at Google Scholar
  3. A. S. Krolewski, “Progressive renal decline: the new paradigm of diabetic nephropathy in type 1 diabetes,” Diabetes Care, vol. 38, pp. 954–962, 2015. View at Google Scholar
  4. R. Amin, B. Widmer, A. T. Prevost et al., “Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study,” British Medical Journal, vol. 336, pp. 697–701, 2008. View at Google Scholar
  5. A. Kowalski, A. Krikorian, and E. V. Lerma, “Diabetes and chronic kidney disease,” Disease-a-Month, vol. 61, pp. 378–386, 2015. View at Publisher · View at Google Scholar · View at Scopus
  6. J. J. Liu, S. C. Lim, L. Y. Yeoh et al., “Ethnic disparities in risk of cardiovascular disease, end-stage renal disease and all-cause mortality: a prospective study among Asian people with type 2 diabetes,” Diabetic Medicine, vol. 33, pp. 332–339, 2016. View at Publisher · View at Google Scholar · View at Scopus
  7. C. C. Lim, B. W. Teo, P. G. Ong et al., “Chronic kidney disease, cardiovascular disease and mortality: a prospective cohort study in a multi-ethnic Asian population,” European Journal of Preventive Cardiology, vol. 22, pp. 1018–1026, 2015. View at Publisher · View at Google Scholar · View at Scopus
  8. K. R. Tuttle, G. L. Bakris, R. W. Bilous et al., “Diabetic kidney disease: a report from an ADA Consensus Conference,” Diabetes Care, vol. 37, pp. 2864–2883, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. E. T. Rosolowsky, J. Skupien, A. M. Smiles et al., “Risk for ESRD in type 1 diabetes remains high despite renoprotection,” Journals of the American Society of Nephrology, vol. 22, pp. 545–553, 2011. View at Google Scholar
  10. R. Saran, Y. Li, B. Robinson et al., “US renal data system 2015 annual data report: epidemiology of kidney disease in the United States,” American Journal of Kidney Diseases, vol. 67, pp. A7–A8, 2016. View at Publisher · View at Google Scholar · View at Scopus
  11. S. B. Ghaderian, F. Hayati, S. Shayanpour, and S. S. Beladi Mousavi, “Diabetes and end-stage renal disease; a review article on new concepts,” Journal of Renal Injury Prevention, vol. 4, pp. 28–33, 2015. View at Google Scholar
  12. H. B. Lee, “Reactive oxygen species-regulated signaling pathways in diabetic nephropathy,” Journal of the American Society of Nephrology, vol. 14, pp. 241S–245S, 2003. View at Google Scholar
  13. K. Susztak, A. C. Raff, M. Schiffer, and E. P. Bottinger, “Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy,” Diabetes, vol. 55, pp. 225–233, 2006. View at Google Scholar
  14. L. E. Fridlyand and L. H. Philipson, “Oxidative reactive species in cell injury: mechanisms in diabetes mellitus and therapeutic approaches,” Annals of the New York Academy of Sciences, vol. 1066, pp. 136–151, 2005. View at Google Scholar
  15. G. Al-Kafaji, M. A. Sabry, and C. Skrypnyk, “Time-course effect of high-glucose-induced reactive oxygen species on mitochondrial biogenesis and function in human renal mesangial cells,” Cell Biology International, vol. 40, pp. 36–48, 2016. View at Google Scholar
  16. L. Sun, R. K. Dutta, P. Xie, and Y. S. Kanwar, “Myo-inositol oxygenase overexpression accentuates generation of reactive oxygen species and exacerbates cellular injury following high glucose ambience: a new mechanism relevant to the pathogenesis of diabetic nephropathy,” The Journal of Biological Chemistry, vol. 291, pp. 5688–5707, 2016. View at Google Scholar
  17. K. Kim, C. M. Oh, M. Ohara-Imaizumi et al., “Functional role of serotonin in insulin secretion in a diet-induced insulin-resistant state,” Endocrinology, vol. 156, pp. 444–452, 2015. View at Publisher · View at Google Scholar · View at Scopus
  18. Q. Zhang, Y. Zhu, W. Zhou, L. Gao, L. Yuan, and X. Han, “Serotonin receptor 2c and insulin secretion,” PLoS One, vol. 8, article e54250, 2013. View at Google Scholar
  19. Y. Ohta, Y. Kosaka, N. Kishimoto et al., “Convergence of the insulin and serotonin programs in the pancreatic beta-cell,” Diabetes, vol. 60, pp. 3208–3216, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. C. M. Oh, J. Namkung, Y. Go et al., “Regulation of systemic energy homeostasis by serotonin in adipose tissues,” Nature Communications, vol. 6, p. 6794, 2015. View at Publisher · View at Google Scholar · View at Scopus
  21. K. A. Rasbach, J. A. Funk, T. Jayavelu, P. T. Green, and R. G. Schnellmann, “5-Hydroxytryptamine receptor stimulation of mitochondrial biogenesis,” The Journal of Pharmacology and Experimental Therapeutics, vol. 332, pp. 632–639, 2010. View at Google Scholar
  22. R. Arreola, E. Becerril-Villanueva, C. Cruz-Fuentes et al., “Immunomodulatory effects mediated by serotonin,” Journal of Immunology Research, vol. 2015, Article ID 354957, 21 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  23. G. P. Ahern, “5-HT and the immune system,” Current Opinion in Pharmacology, vol. 11, pp. 29–33, 2011. View at Google Scholar
  24. G. A. Ramirez, S. Franchini, P. Rovere-Querini, M. G. Sabbadini, A. A. Manfredi, and N. Maugeri, “The role of platelets in the pathogenesis of systemic sclerosis,” Frontiers in Immunology, vol. 3, p. 160, 2012. View at Google Scholar
  25. M. de Las Casas-Engel and A. L. Corbi, “Serotonin modulation of macrophage polarization: inflammation and beyond,” Advances in Experimental Medicine and Biology, vol. 824, pp. 89–115, 2014. View at Google Scholar
  26. M. Idzko, S. Pitchford, and C. Page, “Role of platelets in allergic airway inflammation,” The Journal of Allergy and Clinical Immunology, vol. 135, pp. 1416–1423, 2015. View at Google Scholar
  27. J. J. Worthington, “The intestinal immunoendocrine axis: novel cross-talk between enteroendocrine cells and the immune system during infection and inflammatory disease,” Biochemical Society Transactions, vol. 43, pp. 727–733, 2015. View at Google Scholar
  28. T. Sugiura, Y. Dohi, S. Yamashita, Y. Hirowatari, S. Fujii, and N. Ohte, “Serotonin in peripheral blood reflects oxidative stress and plays a crucial role in atherosclerosis: novel insights toward holistic anti-atherothrombotic strategy,” Atherosclerosis, vol. 246, pp. 157–160, 2016. View at Google Scholar
  29. K. Nonogaki and T. Kaji, “Mosapride, a selective serotonin 5-HT4 receptor agonist, and alogliptin, a selective dipeptidyl peptidase-4 inhibitor, exert synergic effects on plasma active glp-1 levels and glucose tolerance in mice,” Diabetes Research and Clinical Practice, vol. 110, pp. e18–e21, 2015. View at Google Scholar
  30. F. Montastruc, A. Palmaro, H. Bagheri, L. Schmitt, J. L. Montastruc, and M. Lapeyre-Mestre, “Role of serotonin 5-HT2c and histamine h1 receptors in antipsychotic-induced diabetes: a pharmacoepidemiological-pharmacodynamic study in vigibase,” European Neuropsychopharmacology, vol. 25, pp. 1556–1565, 2015. View at Google Scholar
  31. H. Bennet, A. Balhuizen, A. Medina et al., “Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes,” Peptides, vol. 71, pp. 113–120, 2015. View at Publisher · View at Google Scholar · View at Scopus
  32. A. Barzegar-Fallah, H. Alimoradi, F. Asadi, A. R. Dehpour, M. Asgari, and M. Shafiei, “Tropisetron ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats,” Clinical and Experimental Pharmacology & Physiology, vol. 42, pp. 361–368, 2015. View at Google Scholar
  33. S. Kobayashi, M. Satoh, T. Namikoshi et al., “Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy,” Clinical and Experimental Nephrology, vol. 12, pp. 119–125, 2008. View at Google Scholar
  34. T. Takahashi, M. Yano, J. Minami et al., “Sarpogrelate hydrochloride, a serotonin2A receptor antagonist, reduces albuminuria in diabetic patients with early-stage diabetic nephropathy,” Diabetes Research and Clinical Practice, vol. 58, pp. 123–129, 2002. View at Google Scholar
  35. K. Hara, Y. Hirowatari, Y. Shimura, and H. Takahashi, “Serotonin levels in platelet-poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease,” Diabetes Research and Clinical Practice, vol. 94, pp. 167–171, 2011. View at Google Scholar
  36. S. Watanabe, T. Matsumoto, M. Oda et al., “Insulin augments serotonin-induced contraction via activation of the IR/PI3K/PDK1 pathway in the rat carotid artery,” Pflügers Archiv-European Journal of Physiology, vol. 468, no. 4, pp. 667–677, 2016. View at Publisher · View at Google Scholar · View at Scopus
  37. C. M. Oh, S. Park, and H. Kim, “Serotonin as a new therapeutic target for diabetes mellitus and obesity,” Diabetes & Metabolism Journal, vol. 40, pp. 89–98, 2016. View at Google Scholar
  38. K. Hara, Y. Hirowatari, M. Yoshika, Y. Komiyama, Y. Tsuka, and H. Takahashi, “The ratio of plasma to whole-blood serotonin may be a novel marker of atherosclerotic cardiovascular disease,” The Journal of Laboratory and Clinical Medicine, vol. 144, pp. 31–37, 2004. View at Google Scholar
  39. B. A. Davis, A. Nagarajan, L. R. Forrest, and S. K. Singh, “Mechanism of paroxetine (paxil) inhibition of the serotonin transporter,” Scientific Reports, vol. 6, article 23789, 2016. View at Publisher · View at Google Scholar · View at Scopus
  40. J. D. McCorvy and B. L. Roth, “Structure and function of serotonin G protein-coupled receptors,” Pharmacology & Therapeutics, vol. 150, pp. 129–142, 2015. View at Google Scholar
  41. G. Jaim-Etcheverry and L. M. Zieher, “Electron microscopic cytochemistry of 5-hydroxytryptamine (5-HT) in the beta cells of guinea pig endocrine pancreas,” Endocrinology, vol. 83, pp. 917–923, 1968. View at Google Scholar
  42. A. Hameed, M. Ajmal, M. Nasir, and M. Ismail, “Genetic association analysis of serotonin transporter polymorphism (5-HTTLPR) with type 2 diabetes patients of Pakistani population,” Diabetes Research and Clinical Practice, vol. 108, pp. 67–71, 2015. View at Google Scholar
  43. D. R. Gehlert and J. Shaw, “5-Hydroxytryptamine 1A (5HT1A) receptors mediate increases in plasma glucose independent of corticosterone,” European Journal of Pharmacology, vol. 745, pp. 91–97, 2014. View at Google Scholar
  44. E. Ezzeldin, W. A. Souror, T. El-Nahhas, A. N. Soudi, and A. A. Shahat, “Biochemical and neurotransmitters changes associated with tramadol in streptozotocin-induced diabetes in rats,” BioMed Research International, vol. 2014, Article ID 238780, 9 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. Hasegawa, A. Suehiro, S. Higasa, M. Namba, and E. Kakishita, “Enhancing effect of advanced glycation end products on serotonin-induced platelet aggregation in patients with diabetes mellitus,” Thrombosis Research, vol. 107, pp. 319–323, 2002. View at Google Scholar
  46. K. V. Derkach, V. M. Bondareva, O. V. Chistyakova, L. M. Berstein, and A. O. Shpakov, “The effect of long-term intranasal serotonin treatment on metabolic parameters and hormonal signaling in rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes,” International Journal of Endocrinology, vol. 2015, Article ID 245459, 17 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  47. L. Goyvaerts, A. Schraenen, and F. Schuit, “Serotonin competence of mouse beta cells during pregnancy,” Diabetologia, vol. 59, no. 7, pp. 1356–1363, 2016. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Ohara-Imaizumi, H. Kim, M. Yoshida et al., “Serotonin regulates glucose-stimulated insulin secretion from pancreatic beta cells during pregnancy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, pp. 19420–19425, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. N. Paulmann, M. Grohmann, J. P. Voigt et al., “Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation,” PLoS Biology, vol. 7, article e1000229, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. J. D. Crane, R. Palanivel, E. P. Mottillo et al., “Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis,” Nature Medicine, vol. 21, pp. 166–172, 2015. View at Publisher · View at Google Scholar · View at Scopus
  51. E. D. Berglund, C. Liu, J. W. Sohn et al., “Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis,” The Journal of Clinical Investigation, vol. 123, pp. 5061–5070, 2013. View at Google Scholar
  52. E. Colman, J. Golden, M. Roberts, A. Egan, J. Weaver, and C. Rosebraugh, “The FDA’s assessment of two drugs for chronic weight management,” The New England Journal of Medicine, vol. 367, pp. 1577–1579, 2012. View at Google Scholar
  53. O. J. Marston, A. S. Garfield, and L. K. Heisler, “Role of central serotonin and melanocortin systems in the control of energy balance,” European Journal of Pharmacology, vol. 660, pp. 70–79, 2011. View at Google Scholar
  54. D. D. Lam and L. K. Heisler, “Serotonin and energy balance: molecular mechanisms and implications for type 2 diabetes,” Expert Reviews in Molecular Medicine, vol. 9, pp. 1–24, 2007. View at Google Scholar
  55. J. Qiu, C. Xue, M. A. Bosch et al., “Serotonin 5-hydroxytryptamine2C receptor signaling in hypothalamic proopiomelanocortin neurons: role in energy homeostasis in females,” Molecular Pharmacology, vol. 72, pp. 885–896, 2007. View at Google Scholar
  56. J. M. Wade, P. Juneja, A. W. MacKay et al., “Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2C receptors,” Endocrinology, vol. 149, pp. 955–961, 2008. View at Google Scholar
  57. G. Csaba, “Hormones in the immune system and their possible role. A critical review,” Acta Microbiologica et Immunologica Hungarica, vol. 61, pp. 241–260, 2014. View at Google Scholar
  58. S. Zheng, S. Coventry, L. Cai et al., “Renal protection by genetic deletion of the atypical chemokine receptor ACKR2 in diabetic OVE mice,” Journal of Diabetes Research, vol. 2016, Article ID 5362506, 11 pages, 2016. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Chabbi-Achengli, T. Coman, C. Collet et al., “Serotonin is involved in autoimmune arthritis through th17 immunity and bone resorption,” The American Journal of Pathology, vol. 186, pp. 927–937, 2016. View at Google Scholar
  60. D. Hirigoyen, P. I. Burgos, V. Mezzano et al., “Inhibition of angiogenesis by platelets in systemic sclerosis patients,” Arthritis Research & Therapy, vol. 17, p. 332, 2015. View at Google Scholar
  61. P. R. Pereira, M. C. Oliveira-Junior, B. MacKenzie et al., “Exercise reduces lung fibrosis involving serotonin/Akt signaling,” Medicine and Science in Sports and Exercise, vol. 48, no. 7, pp. 1276–1284, 2016. View at Publisher · View at Google Scholar · View at Scopus
  62. G. Ahangari, S. E. Koochak, L. M. Amirabad, and G. D. Deilami, “Investigation of 5-HT2A gene expression in PBMCs of patients with allergic asthma,” Inflammation & Allergy Drug Targets, vol. 14, pp. 60–64, 2015. View at Google Scholar
  63. J. M. Forbes and M. E. Cooper, “Mechanisms of diabetic complications,” Physiological Reviews, vol. 93, pp. 137–188, 2013. View at Google Scholar
  64. K. E. Porter and K. Riches, “The vascular smooth muscle cell: a therapeutic target in type 2 diabetes?” Clinical Science (London, England: 1979), vol. 125, pp. 167–182, 2013. View at Google Scholar
  65. K. Yamada, H. Niki, H. Nagai, M. Nishikawa, and H. Nakagawa, “Serotonin potentiates high-glucose-induced endothelial injury: the role of serotonin and 5-HT2A receptors in promoting thrombosis in diabetes,” Journal of Pharmacological Sciences, vol. 119, pp. 243–250, 2012. View at Google Scholar
  66. T. Matsumoto, S. Watanabe, K. Taguchi, and T. Kobayashi, “Mechanisms underlying increased serotonin-induced contraction in carotid arteries from chronic type 2 diabetic Goto-Kakizaki rats,” Pharmacological Research, vol. 87, pp. 123–132, 2014. View at Google Scholar
  67. S. C. Bir, M. Fujita, A. Marui et al., “New therapeutic approach for impaired arteriogenesis in diabetic mouse hindlimb ischemia,” Circulation Journal: Official Journal of the Japanese Circulation Society, vol. 72, pp. 633–640, 2008. View at Google Scholar
  68. Y. Su, N. Mao, M. Li et al., “Sarpogrelate inhibits the expression of ICAM-1 and monocyte-endothelial adhesion induced by high glucose in human endothelial cells,” Molecular and Cellular Biochemistry, vol. 373, pp. 195–199, 2013. View at Google Scholar
  69. P. M. Nelson, J. S. Harrod, and K. G. Lamping, “5HT(2a) and 5HT(2b) receptors contribute to serotonin-induced vascular dysfunction in diabetes,” Experimental Diabetes Research, vol. 2012, Article ID 398406, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. E. R. Seaquist, “Addressing the burden of diabetes,” The Journal of the American Medical Association, vol. 311, pp. 2267-2268, 2014. View at Google Scholar
  71. C. Mora-Fernandez, V. Dominguez-Pimentel, M. M. de Fuentes, J. L. Gorriz, A. Martinez-Castelao, and J. F. Navarro-Gonzalez, “Diabetic kidney disease: from physiology to therapeutics,” The Journal of Physiology, vol. 592, pp. 3997–4012, 2014. View at Google Scholar
  72. G. Wolf, “New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathology,” European Journal of Clinical Investigation, vol. 34, pp. 785–796, 2004. View at Google Scholar
  73. J. Wang, F. Qin, A. Deng, and L. Yao, “Different localization and expression of protein kinase C-beta in kidney cortex of diabetic nephropathy mice and its role in telmisartan treatment,” American Journal of Translational Research, vol. 7, pp. 1116–1125, 2015. View at Google Scholar
  74. J. Yang and J. Zhang, “Influence of protein kinase C (PKC) on the prognosis of diabetic nephropathy patients,” International Journal of Clinical and Experimental Pathology, vol. 8, pp. 14925–14931, 2015. View at Google Scholar
  75. K. Zhu, T. Kakehi, M. Matsumoto et al., “NADPH oxidase NOX1 is involved in activation of protein kinase C and premature senescence in early stage diabetic kidney,” Free Radical Biology & Medicine, vol. 83, pp. 21–30, 2015. View at Publisher · View at Google Scholar · View at Scopus
  76. J. C. Jha, V. Thallas-Bonke, C. Banal et al., “Podocyte-specific NOX4 deletion affords renoprotection in a mouse model of diabetic nephropathy,” Diabetologia, vol. 59, pp. 379–389, 2016. View at Google Scholar
  77. Y. Gorin, R. C. Cavaglieri, K. Khazim et al., “Targeting NADPH oxidase with a novel dual NOX1/NOX4 inhibitor attenuates renal pathology in type 1 diabetes,” American Journal of Physiology Renal Physiology, vol. 308, pp. F1276–F1287, 2015. View at Publisher · View at Google Scholar · View at Scopus
  78. A. B. Bhatti and M. Usman, “Drug targets for oxidative podocyte injury in diabetic nephropathy,” Cureus, vol. 7, article e393, 2015. View at Google Scholar
  79. S. C. Tang, W. H. Yiu, M. Lin, and K. N. Lai, “Diabetic nephropathy and proximal tubular damage,” Journal of Renal Nutrition: The Official Journal of the Council on Renal Nutrition of the National Kidney Foundation, vol. 25, pp. 230–233, 2015. View at Google Scholar
  80. P. M. Garcia-Garcia, M. A. Getino-Melian, V. Dominguez-Pimentel, and J. F. Navarro-Gonzalez, “Inflammation in diabetic kidney disease,” World Journal of Diabetes, vol. 5, pp. 431–443, 2014. View at Google Scholar
  81. L. Nalysnyk, M. Hernandez-Medina, and G. Krishnarajah, “Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature,” Diabetes, Obesity & Metabolism, vol. 12, pp. 288–298, 2010. View at Google Scholar
  82. W. J. Ni, L. Q. Tang, and W. Wei, “Research progress in signalling pathway in diabetic nephropathy,” Diabetes/Metabolism Research and Reviews, vol. 31, pp. 221–233, 2015. View at Google Scholar
  83. J. Saito, E. Suzuki, Y. Tajima, K. Takami, Y. Horikawa, and J. Takeda, “Increased plasma serotonin metabolite 5-hydroxyindole acetic acid concentrations are associated with impaired systolic and late diastolic forward flows during cardiac cycle and elevated resistive index at popliteal artery and renal insufficiency in type 2 diabetic patients with microalbuminuria,” Endocrine Journal, vol. 63, no. 1, pp. 69–76, 2016. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Fukui, E. Shiraishi, M. Tanaka et al., “Plasma serotonin is a predictor for deterioration of urinary albumin excretion in men with type 2 diabetes mellitus,” Metabolism: Clinical and Experimental, vol. 58, pp. 1076–1079, 2009. View at Google Scholar
  85. M. Kasho, M. Sakai, T. Sasahara et al., “Serotonin enhances the production of type IV collagen by human mesangial cells,” Kidney International, vol. 54, pp. 1083–1092, 1998. View at Google Scholar
  86. J. S. Grewal, L. M. Luttrell, and J. R. Raymond, “G protein-coupled receptors desensitize and down-regulate epidermal growth factor receptors in renal mesangial cells,” The Journal of Biological Chemistry, vol. 276, pp. 27335–27344, 2001. View at Google Scholar
  87. J. S. Grewal, Y. V. Mukhin, M. N. Garnovskaya, J. R. Raymond, and E. L. Greene, “Serotonin 5-HT2A receptor induces TGF-beta1 expression in mesangial cells via ERK: proliferative and fibrotic signals,” The American Journal of Physiology, vol. 276, pp. F922–F930, 1999. View at Google Scholar
  88. N. Pizzinat, J. P. Girolami, A. Parini, C. Pecher, and C. Ordener, “Serotonin metabolism in rat mesangial cells: involvement of a serotonin transporter and monoamine oxidase a,” Kidney International, vol. 56, pp. 1391–1399, 1999. View at Google Scholar
  89. C. G. Nebigil, M. N. Garnovskaya, R. F. Spurney, and J. R. Raymond, “Identification of a rat glomerular mesangial cell mitogenic 5-HT2A receptor,” The American Journal of Physiology, vol. 268, pp. F122–F127, 1995. View at Google Scholar
  90. S. Ogawa, T. Mori, K. Nako, T. Ishizuka, and S. Ito, “Reduced albuminuria with sarpogrelate is accompanied by a decrease in monocyte chemoattractant protein-1 levels in type 2 diabetes,” Clinical Journal of the American Society of Nephrology, vol. 3, pp. 362–368, 2008. View at Google Scholar
  91. S. Y. Park, S. Y. Rhee, S. Oh et al., “Evaluation of the effectiveness of sarpogrelate on the surrogate markers for macrovascular complications in patients with type 2 diabetes,” Endocrine Journal, vol. 59, pp. 709–716, 2012. View at Google Scholar