Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-10T11:48:25.479Z Has data issue: false hasContentIssue false
  • English
  • Français

The complex interactions among serotonin, insulin, leptin, and glycolipid metabolic parameters in human obesity

Published online by Cambridge University Press:  14 September 2020

Donatella Marazziti Open the ORCID record for Donatella Marazziti [Opens in a new window] ,
Laura Betti ,
Stefano Baroni ,
Lionella Palego ,
Federico Mucci Open the ORCID record for Federico Mucci [Opens in a new window] ,
Barbara Carpita Open the ORCID record for Barbara Carpita [Opens in a new window] ,
Ivan Mirco Cremone ,
Ferruccio Santini ,
Laura Fabbrini  and
Caterina Pelosini
...Show all authors
Donatella Marazziti*
Affiliation:
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy Saint Camillus International University of Health and Medical Sciences, Rome, Italy Brain Research Foundation Lucca, Italy
Laura Betti
Affiliation:
Department of Pharmacy, University of Pisa, Italy
Stefano Baroni
Affiliation:
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy
Lionella Palego
Affiliation:
Department of Pharmacy, University of Pisa, Italy
Federico Mucci
Affiliation:
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Italy
Barbara Carpita
Affiliation:
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Italy
Ivan Mirco Cremone
Affiliation:
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy
Ferruccio Santini
Affiliation:
Department of Clinical and Experimental Medicine, Endocrinology Unit, Obesity and Lipodystrophy Centre, University of Pisa, Pisa, Italy
Laura Fabbrini
Affiliation:
Pharmacology and Pharmacogenetics, University Hospital Unit, University of Pisa, Pisa, Italy
Caterina Pelosini
Affiliation:
Department of Clinical and Experimental Medicine, Endocrinology Unit, Obesity and Lipodystrophy Centre, University of Pisa, Pisa, Italy
Alessandro Marsili
Affiliation:
Department of Clinical and Experimental Medicine, Endocrinology Unit, Obesity and Lipodystrophy Centre, University of Pisa, Pisa, Italy
Enrico Massimetti
Affiliation:
ASST, «Servizio Psichiatrico Diagnosi e Cura», Hospital of “Bergamo Ovest”, SSD, Treviglio, Italy
Gino Giannaccini
Affiliation:
Department of Pharmacy, University of Pisa, Italy
Liliana Dell’Osso
Affiliation:
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Italy
*
*Author for correspondence: Donatella Marazziti, MD Email: dmarazzi@psico.med.unipi.it
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

To provide evidence to the link between serotonin (5-HT), energy metabolism, and the human obese phenotype, the present study investigated the binding and function of the platelet 5-HT transporter (SERT), in relation to circulating insulin, leptin, and glycolipid metabolic parameters.

Methods

Seventy-four drug-free subjects were recruited on the basis of divergent body mass index (BMIs) (16.5-54.8 Kg/m2). All subjects were tested for their blood glycolipid profile together with platelet [3H]-paroxetine ([3H]-Par) binding and [3H]-5-HT reuptake measurements from April 1st to June 30th, 2019.

Results

The [3H]-Par Bmax (fmol/mg proteins) was progressively reduced with increasing BMIs (P < .001), without changes in affinity. Moreover, Bmax was negatively correlated with BMI, waist/hip circumferences (W/HC), triglycerides (TD), glucose, insulin, and leptin, while positively with high-density lipoprotein (HDL) cholesterol (P < .01). The reduction of 5-HT uptake rate (Vmax, pmol/min/109 platelets) among BMI groups was not statistically significant, but Vmax negatively correlated with leptin and uptake affinity values (P < .05). Besides, [3H]-Par affinity values positively correlated with glycemia and TD, while [3H]-5-HT reuptake affinity with glycemia only (P < .05). Finally, these correlations were specific of obese subjects, while, from multiple linear-regression analysis conducted on all subjects, insulin (P = .006) resulting negatively related to Bmax independently from BMI.

Conclusions

Present findings suggest the presence of a possible alteration of insulin/5-HT/leptin axis in obesity, differentially impinging the density, function, and/or affinity of the platelet SERT, as a result of complex appetite/reward-related interactions between the brain, gut, pancreatic islets, and adipose tissue. Furthermore, they support the foremost cooperation of peptides and 5-HT in maintaining energy homeostasis.

Keywords

Obesityserotoninserotonin transporterinsulinleptinglycolipid metabolism
Type
Original Research
Information
CNS Spectrums , Volume 27 , Issue 1 , February 2022 , pp. 99 - 108
Copyright
© The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Williams, EP, Mesidor, M, Winters, K, Dubbert, PM, Wyatt, SB. Overweight and obesity: prevalence, consequences, and causes of a growing public health problem. Curr Obes Rep. 2015;4(3):363–370. doi:10.1007/s13679-015-0169-4.CrossRefGoogle ScholarPubMed
Apovian, CM. Obesity: definition, comorbidities, causes, and burden. Am J Manag Care. 2016;22(suppl 7):s176–s185Google ScholarPubMed
GBD 2016 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 [published correction appears in Lancet. 2017;390(10104):1736] [published correction appears in Lancet. 2017;390(10106):e38]. Lancet. 2017;390(10100):1345–1422. doi:10.1016/S0140-6736(17)32366-8.CrossRefGoogle Scholar
Hales, CM, Carroll, MD, Fryar, CD, Ogden, CL. Prevalence of obesity among adults and youth: United States 2015–2016. NCHS Data Brief. 2016;2017(288):1–8.Google Scholar
World Health Organisation. Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed February 29, 2020.Google Scholar
World Health Organisation. Global action plan for the prevention and control of non-communicable diseases 2013–2020. https://www.who.int/nmh/events/ncd_action_plan/en/. Accessed February 29, 2020.Google Scholar
Hruby, A, Hu, FB. The epidemiology of obesity: a big picture. Pharmacoeconomics. 2015;33(7):673–689. doi:10.1007/s40273-014-0243-x.CrossRefGoogle ScholarPubMed
Volkow, ND, Wang, GJ, Baler, RD. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn Sci. 2011;15(1):37–46. doi:10.1016/j.tics.2010.11.001.CrossRefGoogle ScholarPubMed
Field, BC. Neuroendocrinology of obesity. Br Med Bull. 2014;109:73–82. doi:10.1093/bmb/ldu001.CrossRefGoogle ScholarPubMed
Voigt, JP, Fink, H. Serotonin controlling feeding and satiety. Behav Brain Res. 2015;277:14–31. doi:10.1016/j.bbr.2014.08.065.CrossRefGoogle ScholarPubMed
Giannaccini, G, Betti, L, Palego, L, et al. The expression of platelet serotonin transporter (SERT) in human obesity. BMC Neurosci. 2013;14:128. doi: 10.1186/1471-2202-14-128.CrossRefGoogle Scholar
Martin, AM, Young, RL, Leong, L, et al. The diverse metabolic roles of peripheral serotonin. Endocrinology. 2017;158(5):1049–1063. doi:10.1210/en.2016-1839.CrossRefGoogle ScholarPubMed
Wurtman, RJ. Non-nutritional uses of nutrients. Eur J Pharmacol. 2011;668(suppl 1):S10–15. doi:10.1016/j.ejphar.2011.07.005.CrossRefGoogle ScholarPubMed
Fernstrom, JD. Large neutral amino acids: dietary effects on brain neurochemistry and function. Amino Acids. 2013;45(3):419–430. doi:10.1007/s00726-012-1330-y.CrossRefGoogle ScholarPubMed
Peuhkuri, K, Sihvola, N, Korpela, R. Diet promotes sleep duration and quality. Nutr Res. 2012;32(5):309–319. doi:10.1016/j.nutres.2012.03.009.CrossRefGoogle ScholarPubMed
Wyler, SC, Lord, CC, Lee, S, Elmquist, JK, Liu, C. Serotonergic control of metabolic homeostasis. Front Cell Neurosci. 2017;11:277. doi:10.3389/fncel.2017.00277.CrossRefGoogle ScholarPubMed
Kinoshita, M, Ono, K, Horie, T, et al. Regulation of adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of microRNA-448-mediated repression of KLF5. Mol Endocrinol. 2010;24(10):1978–1987. doi:10.1210/me.2010-0054.CrossRefGoogle ScholarPubMed
Stunes, AK, Reseland, JE, Hauso, O, et al. Adipocytes express a functional system for serotonin synthesis, reuptake and receptor activation. Diabetes Obes Metab. 2011;13(6):551–558. doi:10.1111/j.1463-1326.2011.01378.x.CrossRefGoogle ScholarPubMed
Marazziti, D, Rutigliano, G, Baroni, S, Landi, P, Dell’Osso, L. Metabolic syndrome and major depression. CNS Spectr. 2014;19(4):293–304. doi:10.1017/S1092852913000667.CrossRefGoogle ScholarPubMed
Oury, F, Karsenty, G. Towards a serotonin-dependent leptin roadmap in the brain. Trends Endocrinol Metab. 2011;22(9):382–387. doi:10.1016/j.tem.2011.04.006.CrossRefGoogle Scholar
Yadav, VK, Oury, F, Tanaka, KF, et al. Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional regulation, and therapeutic implications [published correction appears in J Exp Med. 2011;208(2):413. Tanaka, Kenji [corrected to Tanaka, Kenji F]]. J Exp Med. 2011;208(1):41–52. doi:10.1084/jem.20101940.CrossRefGoogle ScholarPubMed
Tortorella, A, Brambilla, F, Fabrazzo, M, et al. Central and peripheral peptides regulating eating behaviour and energy homeostasis in anorexia nervosa and bulimia nervosa: a literature review. Eur Eat Disord Rev. 2014;22(5):307–320. doi:10.1002/erv.2303).CrossRefGoogle ScholarPubMed
Stahl, SM. The human platelet. A diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders. Arch Gen Psychiatry. 1977;34(5):509–516. doi:10.1001/archpsyc.1977.01770170019001.CrossRefGoogle Scholar
Marazziti, D, Rossi, A, Giannaccini, G, Baroni, S, Lucacchini, A, Cassano, GB. Presence and characterization of the serotonin transporter in human resting lymphocytes. Neuropsychopharmacology. 1998;19(2):154–159. doi: 10.1016/S0893-133X(97)00204-2.CrossRefGoogle ScholarPubMed
Lesch, KP, Wolozin, BL, Murphy, DL, Reiderer, P. Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem. 1993;60(6):2319–2322. doi:10.1111/j.1471-4159.1993.tb03522.x.CrossRefGoogle ScholarPubMed
Langer, SZ, Galzin, AM, Poirier, MF, Loo, H, Sechter, D, Zarifian, E. Association of [3H]-imipramine and [3H]-paroxetine binding with the 5HT transporter in brain and platelets: relevance to studies in depression. J Recept Res. 1987;7(1–4):499–521. doi: 10.3109/10799898709054999.CrossRefGoogle Scholar
Marazziti, D, Rossi, A, Gemignani, A, et al. Decreased platelet 3H-paroxetine binding in obsessive-compulsive patients. Neuropsychobiology. 1996;34(4):184–187. doi:10.1159/000119308.CrossRefGoogle ScholarPubMed
Marazziti, D, Dell’Osso, L, Rossi, A, et al. Decreased platelet [3H]paroxetine binding sites in suicide attempters. Psychiatry Res. 2001;103(2–3):125–131. doi: 10.1159/000129665.CrossRefGoogle ScholarPubMed
Marazziti, D, Landi, P, Baroni, S, et al. The role of platelet/lymphocyte serotonin transporter in depression and beyond. Curr Drug Targets. 2013;14(5):522–530. doi:10.2174/1389450111314050003.CrossRefGoogle ScholarPubMed
Aharonovitz, O, Granot, Y. Stimulation of mitogen-activated protein kinase and Na+/H+ exchanger in human platelets. Differential effect of phorbol ester and vasopressin. J Biol Chem. 1996;271(28):16494–16499. doi:10.1074/jbc.271.28.16494.CrossRefGoogle ScholarPubMed
Carneiro, AM, Blakely, RD. Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the platelet serotonin transporter. J Biol Chem. 2006;281(34):24769–24780. doi:10.1074/jbc.M603877200.CrossRefGoogle ScholarPubMed
Giannaccini, G, Betti, L, Palego, L, et al. Human serotonin transporter expression during megakaryocytic differentiation of MEG-01 cells. Neurochem Res. 2010;35(4):628–635. doi:10.1007/s11064-009-0112-8.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW. Structured Clinical Interview for DSM-IV Axis I Disorders—Clinican Version (SCID-CV). Washington, DC: American Psychiatric Press; 1997.Google Scholar
Marazziti, D, Falcone, MF, Castrogiovanni, P, Cassano, GB. Seasonal serotonin uptake changes in healthy subjects. Mol Chem Neuropathol. 1990;13(1–2):145–154. doi:10.1007/BF03159915.CrossRefGoogle ScholarPubMed
Arora, RC, Meltzer, HY. Serotonin uptake by blood platelets of schizophrenic patients. Psychiatry Res. 1982;6(3):327–333. doi: 10.1016/0165-1781(82)90022-1.CrossRefGoogle ScholarPubMed
McPherson, GA. Analysis of radioligand binding experiments. A collection of computer programs for the IBM PC. J Pharmacol Methods. 1985;14(3):213–228. doi:10.1016/0160-5402(85)90034-8.CrossRefGoogle ScholarPubMed
Curzon, G. Serotonin and appetite. Ann N Y Acad Sci. 1990;600:521–531. doi:10.1111/j.1749-6632.1990.tb16907.x.CrossRefGoogle ScholarPubMed
Berglund, ED, Liu, C, Sohn, JW, et al. Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis [published correction appears in J Clin Invest. 2014;124(4):1868. Dosage error in article text]. J Clin Invest. 2013;123(12):5061–5070. doi:10.1172/JCI70338.CrossRefGoogle Scholar
Garfield, AS, Heisler, LK. Pharmacological targeting of the serotonergic system for the treatment of obesity. J Physiol. 2009;587(1):49–60. doi:10.1113/jphysiol.2008.164152.CrossRefGoogle ScholarPubMed
Höglund, E, Øverli, Ø, Winberg, S. Tryptophan metabolic pathways and brain serotonergic activity: a comparative review. Front Endocrinol (Lausanne). 2019;10:158. doi:10.3389/fendo.2019.00158.CrossRefGoogle ScholarPubMed
Daws, LC, Gould, GG. Ontogeny and regulation of the serotonin transporter: providing insights into human disorders. Pharmacol Ther. 2011;131(1):61–79. doi:10.1016/j.pharmthera.2011.03.013.CrossRefGoogle ScholarPubMed
Brindley, RL, Bauer, MB, Blakely, RD, Currie, KPM. An interplay between the serotonin transporter (SERT) and 5-HT receptors controls stimulus-secretion coupling in sympathoadrenal chromaffin cells. Neuropharmacology. 2016;110(pt A):438–448. doi:10.1016/j.neuropharm.2016.08.015.CrossRefGoogle ScholarPubMed
El-Merahbi, R, Löffler, M, Mayer, A, Sumara, G. The roles of peripheral serotonin in metabolic homeostasis. FEBS Lett. 2015;589(15):1728–1734. doi:10.1016/j.febslet.2015.05.054.CrossRefGoogle ScholarPubMed
Marazziti, D, Rossi, A, Palego, L, et al. Effect of aging and sex on the [3H]-paroxetine binding to human platelets. J Affect Disord. 1998;50(1):11–15. doi:10.1016/s0165-0327(97)00074-8.CrossRefGoogle ScholarPubMed
Fond, G, Young, AH, Godin, O, et al. Improving diet for psychiatric patients: High potential benefits and evidence for safety. J Affect Disord. 2020;265:567–569. doi:10.1016/j.jad.2019.11.092.CrossRefGoogle ScholarPubMed
Shafiei, F, Salari-Moghaddam, A, Larijani, B, Esmaillzadeh, A. Adherence to the Mediterranean diet and risk of depression: a systematic review and updated meta-analysis of observational studies [published correction appears in Nutr Rev. 2019;77(6):454]. Nutr Rev. 2019;77(4):230–239. doi:10.1093/nutrit/nuy070.CrossRefGoogle Scholar
Erritzoe, D, Frokjaer, VG, Haahr, MT, et al. Cerebral serotonin transporter binding is inversely related to body mass index. Neuroimage. 2010;52(1):284–289. doi:10.1016/j.neuroimage.2010.03.086.CrossRefGoogle ScholarPubMed
Rajan, TM, Menon, V. Psychiatric disorders and obesity: a review of association studies. J Postgrad Med. 2017;63(3):182–190. doi:10.4103/jpgm.JPGM_712_16.Google ScholarPubMed
Navab, M, Reddy, ST, Van Lenten, BJ, Fogelman, AM. HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nat Rev Cardiol. 2011;8(4):222–232. doi:10.1038/nrcardio.2010.222.CrossRefGoogle ScholarPubMed
Rytter, E, Vessby, B, Asgård, R, et al. Glycaemic status in relation to oxidative stress and inflammation in well-controlled type 2 diabetes subjects. Br J Nutr. 2009;101(10):1423–1426. doi:10.1017/s0007114508076204.CrossRefGoogle ScholarPubMed
Norata, GD, Pirillo, A, Ammirati, E, Catapano, AL. Emerging role of high-density lipoproteins as a player in the immune system. Atherosclerosis. 2012;220(1):11–21. doi:10.1016/j.atherosclerosis.2011.06.045.CrossRefGoogle ScholarPubMed
Holven, KB, Retterstol, K, Ueland, T, et al. Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype. PLoS One. 2013;8(11):e78241. doi:10.1371/journal.pone.0078241.CrossRefGoogle ScholarPubMed
Maes, M, Yirmyia, R, Noraberg, J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009;24(1):27–53. doi:10.1007/s11011-008-9118-1.CrossRefGoogle ScholarPubMed
Zunszain, PA, Hepgul, N, Pariante, CM. Inflammation and depression. Curr Top Behav Neurosci. 2013;14:135–151. doi:10.1007/7854_2012_211.CrossRefGoogle ScholarPubMed
Felger, JC. Imaging the role of inflammation in mood and anxiety-related disorders. Curr Neuropharmacol. 2018;16(5):533–558. doi:10.2174/1570159X15666171123201142.CrossRefGoogle Scholar
Zuccoli, GS, Saia-Cereda, VM, Nascimento, JM, Martins-de-Souza, D. The energy metabolism dysfunction in psychiatric disorders postmortem brains: focus on proteomic evidence. Front Neurosci. 2017;11:493. doi:10.3389/fnins.2017.00493.CrossRefGoogle ScholarPubMed
Iikuni, N, Lam, QL, Lu, L, Matarese, G, La Cava, A. Leptin and inflammation. Curr Immunol Rev. 2008;4(2):70–79. doi:10.2174/157339508784325046.CrossRefGoogle ScholarPubMed
Taylor, VH, Macqueen, GM. The role of adipokines in understanding the associations between obesity and depression. J Obes. 2010;2010:748048. doi:10.1155/2010/748048.CrossRefGoogle ScholarPubMed
Chehab, FF. Leptin as a regulator of adipose mass and reproduction. Trends Pharmacol Sci. 2000;21(8):309–314. doi:10.1016/s0165-6147(00)01514-5.CrossRefGoogle ScholarPubMed
Jéquier, E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci. 2002;967:379–388. doi:10.1111/j.1749-6632.2002.tb04293.x.CrossRefGoogle ScholarPubMed
Giannaccini, G, Betti, L, Palego, L, et al. Serotonin transporter (SERT) and translocator protein (TSPO) expression in the obese ob/ob mouse. BMC Neurosci. 2011;12:18. doi:10.1186/1471-2202-12-18.CrossRefGoogle ScholarPubMed
Considine, RV, Sinha, MK, Heiman, ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334(5):292–295. doi:10.1056/NEJM199602013340503.CrossRefGoogle ScholarPubMed
Heymsfield, SB, Greenberg, AS, Fujioka, K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA. 1999;282(16):1568–1575. doi:10.1001/jama.282.16.1568.CrossRefGoogle ScholarPubMed
Zhou, Y, Rui, L. Leptin signaling and leptin resistance. Front Med. 2013;7(2):207–222. doi:10.1007/s11684-013-0263-5.CrossRefGoogle ScholarPubMed
Milaneschi, Y, Lamers, F, Bot, M, Drent, ML, Penninx, BW. Leptin dysregulation is specifically associated with major depression with atypical features: evidence for a mechanism connecting obesity and depression. Biol Psychiatry. 2017;81(9):807–814. doi:10.1016/j.biopsych.2015.10.023.CrossRefGoogle ScholarPubMed
Sinha, R, Jastreboff, AM. Stress as a common risk factor for obesity and addiction. Biol Psychiatry. 2013;73(9):827–835. doi:10.1016/j.biopsych.2013.01.032.CrossRefGoogle ScholarPubMed
Tomiyama, AJ. Stress and obesity. Annu Rev Psychol. 2019;70:703–718. doi:10.1146/annurev-psych-010418-102936.CrossRefGoogle ScholarPubMed
Pratt, WE, Schall, MA, Choi, E. Selective serotonin receptor stimulation of the medial nucleus accumbens differentially affects appetitive motivation for food on a progressive ratio schedule of reinforcement. Neurosci Lett. 2012;511(2):84–88. doi:10.1016/j.neulet.2012.01.038.CrossRefGoogle ScholarPubMed
Ohta, Y, Kosaka, Y, Kishimoto, N, et al. Convergence of the insulin and serotonin programs in the pancreatic β-cell. Diabetes. 2011;60(12):3208–3216. doi:10.2337/db10-1192.CrossRefGoogle ScholarPubMed
Paulmann, N, Grohmann, M, Voigt, JP, et al. Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation. PLoS Biol. 2009;7(10):e1000229. doi:10.1371/journal.pbio.1000229.CrossRefGoogle ScholarPubMed
Webb, M, Davies, M, Ashra, N, et al. The association between depressive symptoms and insulin resistance, inflammation and adiposity in men and women. PLoS One. 2017;12(11):e0187448. doi:10.1371/journal.pone.0187448.CrossRefGoogle ScholarPubMed
Lu, XY. The leptin hypothesis of depression: a potential link between mood disorders and obesity? Curr Opin Pharmacol. 2007;7(6):648–652. doi:10.1016/j.coph.2007.10.010.CrossRefGoogle ScholarPubMed
Yabut, JM, Crane, JD, Green, AE, Keating, DJ, Khan, WI, Steinberg, GR. Emerging roles for serotonin in regulating metabolism: new implications for an ancient molecule. Endocr Rev. 2019;40(4):1092–1107. doi:10.1210/er.2018-00283.CrossRefGoogle ScholarPubMed
Cataldo Bascuñan, LR, Lyons, C, Bennet, H, Artner, I, Fex, M. Serotonergic regulation of insulin secretion. Acta Physiol (Oxf). 2019;225(1):e13101. doi:10.1111/apha.13101.CrossRefGoogle ScholarPubMed