5-羟色胺对糖尿病糖代谢及其并发症调控作用的研究进展
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摘要
糖尿病是以血糖升高为主要特征的慢性代谢性疾病,1型和2型糖尿病的发病机制有所不同。5-羟色胺既存在于中枢神经系统也存在于外周组织,参与机体正常生理功能和病理调控。近年来对糖尿病发病机制的深入研究,5-羟色胺也被视为重要的潜在调控靶点之一。5-羟色胺对血糖调节有重要作用,对部分糖尿病并发症有调控作用。然而,5-羟色胺调控作用的受体特异性、活动依赖性及其受体分布的组织特异性决定了其调控作用的复杂性。
Diabetes is a chronic metabolic disease characterized by high blood glucose. The mechanisms underlying type 1 and type 2 of diabetes mellitus are different. 5-Hydroxytryptamine( 5-HT),located in central nervous system and peripheral tissues,plays important roles in physiological and pathological functions. Recent evidence indicates 5-HT is considered to be a potential target for treating diabetes and its complications along with deepening of the researches on the mechanisms of diabetes. 5-HT plays an important role in regulating blood glucose and diabetic complications. However,5-HT regulatory role is complicated due to its receptor-specific,activity-dependent and tissue-specific characteristics.
Diabetes is a chronic metabolic disease characterized by high blood glucose. The mechanisms underlying type 1 and type 2 of diabetes mellitus are different. 5-Hydroxytryptamine( 5-HT),located in central nervous system and peripheral tissues,plays important roles in physiological and pathological functions. Recent evidence indicates 5-HT is considered to be a potential target for treating diabetes and its complications along with deepening of the researches on the mechanisms of diabetes. 5-HT plays an important role in regulating blood glucose and diabetic complications. However,5-HT regulatory role is complicated due to its receptor-specific,activity-dependent and tissue-specific characteristics.
引文
[1]Kokil GR,Veedu RN,Ramm GA,et al.Type 2 diabetes mellitus:Limitations of conventional therapies and intervention with nucleic acid-based therapeutics[J].Chem Rev,2015,115(11):4719-4743.
[2]Swami T,Weber HC.Updates on the biology of serotonin and tryptophan hydroxylase[J].Curr Opin Endocrinol Diabetes Obes,2018,25(1):12-21.
[3]Forbes JM,Cooper ME.Mechanisms of diabetic complications[J].Physiol Rev,2013,93(1):137-188.
[4]Regazzi R.MicroRNAs as therapeutic targets for the treatment of diabetes mellitus and its complications[J].Expert Opin Ther Targets,2018,22(2):153-160.
[5]Hernández C,Simó-Servat A,Bogdanov P,et al.Diabetic retinopathy:New therapeutic perspectives based on pathogenic mechanisms[J].J Endocrinol Invest,2017,40(9):925-935.
[6]Oh CM,Park S,Kim H.Serotonin as a new therapeutic target for diabetes mellitus and obesity[J].Diabetes Metab J,2016,40(2):89-98.
[7]Janeway TC,Richardson HB,Park EA.Experiments on the vasoconstrictor action of blood serum[J].Arch Intern Med,1918,21:565-603.
[8]Erspamer V,Asero B.Identification of enteramine,the specific hormone of the enterochromaffin cell system,as 5-hydroxytryptamine[J].Nature,1952,169(4306):800-801.
[9]Brodie BB,Shore PA.A concept for a role of serotonin and norepinephrine as chemical mediators in the brain[J].Ann N Y Acad Sci,1957,66(3):631-642.
[10]Shajib MS,Khan WI.The role of serotonin and its receptors in activation of immune responses and inflammation[J].Acta Physiol(Oxf),2015,213(3):561-574.
[11]El-Salhy M,Gundersen D,Hatlebakk JG,et al.High densities of serotonin and peptide YY cells in the colon of patients with lymphocytic colitis[J].World J Gastroenterol,2012,18(42):6070-6075.
[12]Lyubashina OA,Sivachenko IB.The 5-HT4receptor-mediated inhibition of visceral nociceptive neurons in the rat caudal ventrolateral medulla[J].Neuroscience,2017,359:277-288.
[13]Camilleri M,Boeckxstaens G.Dietary and pharmacological treatment of abdominal pain in IBS[J].Gut,2017,66(5):966-974.
[14]Mawe GM,Hoffman JM.Serotonin signaling in the gut-functions,dysfunctions and therapeutic targets[J].Nat Rev Gastroenterol Hepatol,2013,10(10):473-486.
[15]Tzirogiannis KN,Kourentzi KT,Zyga S,et al.Effect of 5-HT7receptor blockade on liver regeneration after 60-70%partial hepatectomy[J].BMC Gastroenterol,2014,14:201.
[16]Barreiro-Iglesias A,Mysiak KS,Scott AL,et al.Serotonin promotes development and regeneration of spinal motor neurons in zebrafish[J].Cell Rep,2015,13(5):924-932.
[17]Liu MT,Kuan YH,Wang J,et al.5-HT4receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice[J].J Neurosci,2009,29(31):9683-9699.
[18]Bianco F,Bonora E,Natarajan D,et al.Prucalopride exerts neuroprotection in human enteric neurons[J].Am J Physiol Gastrointest Liver Physiol,2016,310(10):G768-775.
[19]Berends AC,Luiten PG,Nyakas C.A review of the neuroprotective properties of the 5-HT1Areceptor agonist repinotan HCl(BAYx3702)in ischemic stroke[J].CNS Drug Rev,2005,11(4):379-402.
[20]Crane JD,Palanivel R,Mottillo EP,et al.Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis[J].Nat Med,2015,21(2):166-72.
[21]Park KR,Kim EC,Hong JT,et al.Dysregulation of 5-hydroxytryptamine 6 receptor accelerates maturation of bone-resorbing osteoclasts and induces bone loss[J].Theranostics,2018,8(11):3087-3098.
[22]Hara K,Hirowatari Y,Shimura Y,et al.Serotonin levels in platelet-poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease[J].Diabetes Res Clin Pract,2011,94(2):167-171.
[23]Takahara H,Fujimura M,Taniguchi S,et al.Changes in serotonin levels and 5-HT receptor activity in duodenum of streptozotocindiabetic rats[J].Am J Physio Gastrointest Liver Physiol,2001,281(3):G798-808.
[24]Abraham PM,Anju TR,Jayanarayanan S,et al.Serotonergic receptor upregulation in cerebral cortex and down regulation in brainstem of streptozotocin induced diabetic rats:Antagonism by pyridoxine and insulin[J].Neurosci Lett,2010,483(1):23-27.
[25]Elbatsh MM.Antidepressant-like effect of simvastatin in diabetic rats[J].Can J Physiol Pharmacol,2015,93(8):649-656.
[26]Umrani DN,Bodiwala DN,Goyal RK.Effect of sarpogrelate on altered STZ-diabetes induced cardiovascular responses to5-hydroxytryptamine in rats[J].Mol Cell Biochem,2003,249(1/2):53-57.
[27]Takishita E,Takahashi A,Harada N,et al.Effect of sarpogrelate hydrochloride,a 5-HT2blocker,on insulin resistance in Otsuka Long Evans Tokushima fatty rats(OLETF rats),a type 2 diabetic rat model[J].J Cardiovasc Pharmacol,2004,43(2):266-270.
[28]李涛,傅继华,王天莹.外周5-羟色胺在胰岛素抵抗中的作用研究进展[J].药学进展,2015,39(2):113-118.
[29]Yamada J,Sugimoto Y,Yoshikawa T,et al.The involvement of the peripheral 5-HT2Areceptor in peripherally administered serotonininduced hyperglycemia in rats[J].Life Sci,1995,57(8):819-825.
[30]Watanabe H,Nakano T,Saito R,et al.Serotonin improves high fat diet induced obesity in mice[J].PLo S One,2016,11(1):e0147143.
[31]Derkach KV,Bondareva VM,Chistyakova OV,et al.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[J].Int J Endocrinol,2015,2015:245459.
[32]Chi TC,Ho YJ,Chen WP,et al.Serotonin enhancesβ-endorphin secretion to lower plasma glucose in streptozotocin-induced diabetic rats[J].Life Sci,2007,80(20):1832-1838.
[33]Ueno N,Satoh Y.Rapid effect of mosapride citrate,5-HT4receptor agonist,on fasting blood glucose in Type 2 diabetes patients[J].J Diabetes Complications,2009,23(4):255-256.
[34]Paulmann N,Grohmann M,Voigt JP,et al.Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation[J].PLo S Biol,2009,7(10):e1000229.
[35]Tudhope SJ,Wang CC,Petrie JL,et al.A novel mechanism for regulating hepatic glycogen synthesis involving serotonin and cyclin-dependent kinase-5[J].Diabetes,2012,61(1):49-60.
[36]Hasni Ebou M,Singh-Estivalet A,Launay JM,et al.Glucocorticoids inhibit basal and hormone-induced serotonin synthesis in pancreatic beta cells[J].PLo S One,2016,11(2):e0149343.
[37]Kim K,Oh CM,Ohara-Imaizumi M,et al.Functional role of serotonin in insulin secretion in a diet-induced insulin-resistant state[J].Endocrinology,2015,156(2):444-452.
[38]Crowell MD,Mathis C,Schettler VA,et al.The effects of tegaserod,a 5-HT4receptor agonist,on gastric emptying in a murine model of diabetes mellitus[J].Neurogastroenterol Motil,2005,17(5):738-743.
[39]Tu H,Cao N,Gu B,et al.Serotonin(5-HT)2 A/2 Creceptor agonist(2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride(DOI)improves voiding efficiency in the diabetic rat[J].BJU Int,2015,116(1):147-155.
[40]Cao N,Huang J,Ni J,et al.Streptozotocin-induced diabetes causes upregulation of serotonin(5-HT)2A/Creceptorsin lumbosacral cord motoneurons and down regulation of serotonergic paraneurons in the urethra[J].Brain Res,2019,1715:21-26.
[41]Bir SC,Fujita M,Marui A,et al.New therapeutic approach for impaired arteriogenesis in diabetic mouse hindlimb ischemia[J].Cir J,2008,72(4):633-640.
[42]Nelson PM,Harrod JS,Lamping KG.5HT2 Aand 5 HT2 Breceptors contribute to serotonin-induced vascular dysfunction in diabetes[J].Exp Diabetes Res,2012,2012:398406.
[43]Shiba T,Yokota A,Gamoh S,et al.Diabetes mellitus induces hyperreactivity of 5-hydroxytryptamine(5-HT)-induced constriction in human internal thoracic artery and is associated with increase in the membrane protein level of 5-HT2Areceptor[J].Biol Pharm Bull,2018,41(5):820-823.
[44]Goldstein DJ,Lu Y,Detke MJ,et al.Duloxetine vs.placebo in patients with painful diabetic neuropathy[J].Pain,2005,116(1/2):109-118.
[45]Mixcoatl-Zecuatl T,Jolivalt CG.A spinal mechanism of action for duloxetine in a rat model of painful diabetic neuropathy[J].Br JPharmacol,2011,164(1):159-169.
[46]Tomic MA,Pecikoza UB,Micov AM,et al.The efficacy of eslicarbazepine acetate in models of trigeminal,neuropathic,and visceral pain:the involvement of 5-HT1B/1Dserotonergic and CB1/CB2cannabinoid receptors[J].Anesth Analg,2015,121(6):1632-1639.
[47]Bekta N,Arslan R,Ozturk Y.Zonisamide:Antihyperalgesic efficacy,the role of serotonergic receptors on efficacy in a rat model for painful diabetic neuropathy[J].Life Sci,2014,95(1):9-13.
[48]Saat K,Koaczkowski M,Furgaa A,et al.Antinociceptive,antiallodynic and antihyperalgesic effects of the 5-HT1Areceptor selective agonist,NLX-112 in mouse models of pain[J].Neuropharmacology,2017,125:181-188.
[49]Bˇadescu SV,Tˇataru C,Kobylinska L,et al.The association between diabetes mellitus and depression[J].J Med Life,2016,9(2):120-125.
[50]Gupta D,Kurhe Y,Radhakrishnan M.Antidepressant effects of insulin in streptozotocin induced diabetic mice:Modulation of brain serotonin system[J].Physiol Behav,2014,129:73-78.
[51]Gupta D,Radhakrishnan M,Kurhe Y.Ondansetron,a 5HT3receptor antagonist reverses depression and anxiety-like behavior in streptozotocin-induced diabetic mice:Possible implication of serotonergic system[J].Eur J Pharmacol,2014,744:59-66.
[52]Saito J,Suzuki E,Tajima Y,et al.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[J].Endocr J,2016,63(1):69-76.
[53]Kobayashi S,Satoh M,Namikoshi T,et al.Blockade of serotonin2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy[J].Clin Exp Nephrol,2008,12:119-125.
[54]Takahashi T,Yano M,Minami J,et al.Sarpogrelate hydrochloride,a serotonin2A receptor antagonist,reduces albuminuria in diabetic patients with early-stage diabetic nephropathy[J].Diabetes Res Clin Pract,2002,58:123-129.
[55]Barzegar-Fallah A,Alimoradi H,Asadi F,et al.Tropisetron ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats[J].Clin Exp Pharmacol Physiol,2015,42:361-368.
[56]Fu J,Li C,Zhang G,et al.Crucial roles of 5-HT and 5-HT2receptor in diabetes-related lipid accumulation and pro-inflammatory cytokine generation in hepatocytes[J].Cell Physiol Biochem,2018,48(6):2409-2428.
[2]Swami T,Weber HC.Updates on the biology of serotonin and tryptophan hydroxylase[J].Curr Opin Endocrinol Diabetes Obes,2018,25(1):12-21.
[3]Forbes JM,Cooper ME.Mechanisms of diabetic complications[J].Physiol Rev,2013,93(1):137-188.
[4]Regazzi R.MicroRNAs as therapeutic targets for the treatment of diabetes mellitus and its complications[J].Expert Opin Ther Targets,2018,22(2):153-160.
[5]Hernández C,Simó-Servat A,Bogdanov P,et al.Diabetic retinopathy:New therapeutic perspectives based on pathogenic mechanisms[J].J Endocrinol Invest,2017,40(9):925-935.
[6]Oh CM,Park S,Kim H.Serotonin as a new therapeutic target for diabetes mellitus and obesity[J].Diabetes Metab J,2016,40(2):89-98.
[7]Janeway TC,Richardson HB,Park EA.Experiments on the vasoconstrictor action of blood serum[J].Arch Intern Med,1918,21:565-603.
[8]Erspamer V,Asero B.Identification of enteramine,the specific hormone of the enterochromaffin cell system,as 5-hydroxytryptamine[J].Nature,1952,169(4306):800-801.
[9]Brodie BB,Shore PA.A concept for a role of serotonin and norepinephrine as chemical mediators in the brain[J].Ann N Y Acad Sci,1957,66(3):631-642.
[10]Shajib MS,Khan WI.The role of serotonin and its receptors in activation of immune responses and inflammation[J].Acta Physiol(Oxf),2015,213(3):561-574.
[11]El-Salhy M,Gundersen D,Hatlebakk JG,et al.High densities of serotonin and peptide YY cells in the colon of patients with lymphocytic colitis[J].World J Gastroenterol,2012,18(42):6070-6075.
[12]Lyubashina OA,Sivachenko IB.The 5-HT4receptor-mediated inhibition of visceral nociceptive neurons in the rat caudal ventrolateral medulla[J].Neuroscience,2017,359:277-288.
[13]Camilleri M,Boeckxstaens G.Dietary and pharmacological treatment of abdominal pain in IBS[J].Gut,2017,66(5):966-974.
[14]Mawe GM,Hoffman JM.Serotonin signaling in the gut-functions,dysfunctions and therapeutic targets[J].Nat Rev Gastroenterol Hepatol,2013,10(10):473-486.
[15]Tzirogiannis KN,Kourentzi KT,Zyga S,et al.Effect of 5-HT7receptor blockade on liver regeneration after 60-70%partial hepatectomy[J].BMC Gastroenterol,2014,14:201.
[16]Barreiro-Iglesias A,Mysiak KS,Scott AL,et al.Serotonin promotes development and regeneration of spinal motor neurons in zebrafish[J].Cell Rep,2015,13(5):924-932.
[17]Liu MT,Kuan YH,Wang J,et al.5-HT4receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice[J].J Neurosci,2009,29(31):9683-9699.
[18]Bianco F,Bonora E,Natarajan D,et al.Prucalopride exerts neuroprotection in human enteric neurons[J].Am J Physiol Gastrointest Liver Physiol,2016,310(10):G768-775.
[19]Berends AC,Luiten PG,Nyakas C.A review of the neuroprotective properties of the 5-HT1Areceptor agonist repinotan HCl(BAYx3702)in ischemic stroke[J].CNS Drug Rev,2005,11(4):379-402.
[20]Crane JD,Palanivel R,Mottillo EP,et al.Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis[J].Nat Med,2015,21(2):166-72.
[21]Park KR,Kim EC,Hong JT,et al.Dysregulation of 5-hydroxytryptamine 6 receptor accelerates maturation of bone-resorbing osteoclasts and induces bone loss[J].Theranostics,2018,8(11):3087-3098.
[22]Hara K,Hirowatari Y,Shimura Y,et al.Serotonin levels in platelet-poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease[J].Diabetes Res Clin Pract,2011,94(2):167-171.
[23]Takahara H,Fujimura M,Taniguchi S,et al.Changes in serotonin levels and 5-HT receptor activity in duodenum of streptozotocindiabetic rats[J].Am J Physio Gastrointest Liver Physiol,2001,281(3):G798-808.
[24]Abraham PM,Anju TR,Jayanarayanan S,et al.Serotonergic receptor upregulation in cerebral cortex and down regulation in brainstem of streptozotocin induced diabetic rats:Antagonism by pyridoxine and insulin[J].Neurosci Lett,2010,483(1):23-27.
[25]Elbatsh MM.Antidepressant-like effect of simvastatin in diabetic rats[J].Can J Physiol Pharmacol,2015,93(8):649-656.
[26]Umrani DN,Bodiwala DN,Goyal RK.Effect of sarpogrelate on altered STZ-diabetes induced cardiovascular responses to5-hydroxytryptamine in rats[J].Mol Cell Biochem,2003,249(1/2):53-57.
[27]Takishita E,Takahashi A,Harada N,et al.Effect of sarpogrelate hydrochloride,a 5-HT2blocker,on insulin resistance in Otsuka Long Evans Tokushima fatty rats(OLETF rats),a type 2 diabetic rat model[J].J Cardiovasc Pharmacol,2004,43(2):266-270.
[28]李涛,傅继华,王天莹.外周5-羟色胺在胰岛素抵抗中的作用研究进展[J].药学进展,2015,39(2):113-118.
[29]Yamada J,Sugimoto Y,Yoshikawa T,et al.The involvement of the peripheral 5-HT2Areceptor in peripherally administered serotonininduced hyperglycemia in rats[J].Life Sci,1995,57(8):819-825.
[30]Watanabe H,Nakano T,Saito R,et al.Serotonin improves high fat diet induced obesity in mice[J].PLo S One,2016,11(1):e0147143.
[31]Derkach KV,Bondareva VM,Chistyakova OV,et al.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[J].Int J Endocrinol,2015,2015:245459.
[32]Chi TC,Ho YJ,Chen WP,et al.Serotonin enhancesβ-endorphin secretion to lower plasma glucose in streptozotocin-induced diabetic rats[J].Life Sci,2007,80(20):1832-1838.
[33]Ueno N,Satoh Y.Rapid effect of mosapride citrate,5-HT4receptor agonist,on fasting blood glucose in Type 2 diabetes patients[J].J Diabetes Complications,2009,23(4):255-256.
[34]Paulmann N,Grohmann M,Voigt JP,et al.Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation[J].PLo S Biol,2009,7(10):e1000229.
[35]Tudhope SJ,Wang CC,Petrie JL,et al.A novel mechanism for regulating hepatic glycogen synthesis involving serotonin and cyclin-dependent kinase-5[J].Diabetes,2012,61(1):49-60.
[36]Hasni Ebou M,Singh-Estivalet A,Launay JM,et al.Glucocorticoids inhibit basal and hormone-induced serotonin synthesis in pancreatic beta cells[J].PLo S One,2016,11(2):e0149343.
[37]Kim K,Oh CM,Ohara-Imaizumi M,et al.Functional role of serotonin in insulin secretion in a diet-induced insulin-resistant state[J].Endocrinology,2015,156(2):444-452.
[38]Crowell MD,Mathis C,Schettler VA,et al.The effects of tegaserod,a 5-HT4receptor agonist,on gastric emptying in a murine model of diabetes mellitus[J].Neurogastroenterol Motil,2005,17(5):738-743.
[39]Tu H,Cao N,Gu B,et al.Serotonin(5-HT)2 A/2 Creceptor agonist(2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride(DOI)improves voiding efficiency in the diabetic rat[J].BJU Int,2015,116(1):147-155.
[40]Cao N,Huang J,Ni J,et al.Streptozotocin-induced diabetes causes upregulation of serotonin(5-HT)2A/Creceptorsin lumbosacral cord motoneurons and down regulation of serotonergic paraneurons in the urethra[J].Brain Res,2019,1715:21-26.
[41]Bir SC,Fujita M,Marui A,et al.New therapeutic approach for impaired arteriogenesis in diabetic mouse hindlimb ischemia[J].Cir J,2008,72(4):633-640.
[42]Nelson PM,Harrod JS,Lamping KG.5HT2 Aand 5 HT2 Breceptors contribute to serotonin-induced vascular dysfunction in diabetes[J].Exp Diabetes Res,2012,2012:398406.
[43]Shiba T,Yokota A,Gamoh S,et al.Diabetes mellitus induces hyperreactivity of 5-hydroxytryptamine(5-HT)-induced constriction in human internal thoracic artery and is associated with increase in the membrane protein level of 5-HT2Areceptor[J].Biol Pharm Bull,2018,41(5):820-823.
[44]Goldstein DJ,Lu Y,Detke MJ,et al.Duloxetine vs.placebo in patients with painful diabetic neuropathy[J].Pain,2005,116(1/2):109-118.
[45]Mixcoatl-Zecuatl T,Jolivalt CG.A spinal mechanism of action for duloxetine in a rat model of painful diabetic neuropathy[J].Br JPharmacol,2011,164(1):159-169.
[46]Tomic MA,Pecikoza UB,Micov AM,et al.The efficacy of eslicarbazepine acetate in models of trigeminal,neuropathic,and visceral pain:the involvement of 5-HT1B/1Dserotonergic and CB1/CB2cannabinoid receptors[J].Anesth Analg,2015,121(6):1632-1639.
[47]Bekta N,Arslan R,Ozturk Y.Zonisamide:Antihyperalgesic efficacy,the role of serotonergic receptors on efficacy in a rat model for painful diabetic neuropathy[J].Life Sci,2014,95(1):9-13.
[48]Saat K,Koaczkowski M,Furgaa A,et al.Antinociceptive,antiallodynic and antihyperalgesic effects of the 5-HT1Areceptor selective agonist,NLX-112 in mouse models of pain[J].Neuropharmacology,2017,125:181-188.
[49]Bˇadescu SV,Tˇataru C,Kobylinska L,et al.The association between diabetes mellitus and depression[J].J Med Life,2016,9(2):120-125.
[50]Gupta D,Kurhe Y,Radhakrishnan M.Antidepressant effects of insulin in streptozotocin induced diabetic mice:Modulation of brain serotonin system[J].Physiol Behav,2014,129:73-78.
[51]Gupta D,Radhakrishnan M,Kurhe Y.Ondansetron,a 5HT3receptor antagonist reverses depression and anxiety-like behavior in streptozotocin-induced diabetic mice:Possible implication of serotonergic system[J].Eur J Pharmacol,2014,744:59-66.
[52]Saito J,Suzuki E,Tajima Y,et al.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[J].Endocr J,2016,63(1):69-76.
[53]Kobayashi S,Satoh M,Namikoshi T,et al.Blockade of serotonin2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy[J].Clin Exp Nephrol,2008,12:119-125.
[54]Takahashi T,Yano M,Minami J,et al.Sarpogrelate hydrochloride,a serotonin2A receptor antagonist,reduces albuminuria in diabetic patients with early-stage diabetic nephropathy[J].Diabetes Res Clin Pract,2002,58:123-129.
[55]Barzegar-Fallah A,Alimoradi H,Asadi F,et al.Tropisetron ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats[J].Clin Exp Pharmacol Physiol,2015,42:361-368.
[56]Fu J,Li C,Zhang G,et al.Crucial roles of 5-HT and 5-HT2receptor in diabetes-related lipid accumulation and pro-inflammatory cytokine generation in hepatocytes[J].Cell Physiol Biochem,2018,48(6):2409-2428.