TABLE 1.

Summary of the role of serotonergic system in diabetes and its complication.

Serotonergic system	Target	Effects	References
Intestine-secreted 5-HT	5-HT2B receptor in hepatocytes	Increases gluconeogenesis, increases serum glucose level	Sumara et al., 2012
		Inhibits glucose uptake into hepatocytes via glucose transporter 2 to increase serum glucose level	Sumara et al., 2012
8-hydroxy-2-(di-n-propylamino)tetralin 5-HT1A receptor agonist	Central nervous system	Increased corticosterone leads to increased plasma glucose levels	Gehlert and Shaw, 2014
5-carboxamidotryptamine Peripherally acting nonselective 5-HT receptor agonist	Peripherally 5-HT7 receptor (>0.05 mg/kg)	Hyperglycemia in rats	Yamada et al., 1998
Mirtazapine 5-HT2 receptor antagonists	Peripheral	Worsens insulin sensitivity	Gilles et al., 2005
Fluoxetine Selective serotonin reuptake inhibitor	Peripheral	Ameliorates insulin sensitivity	Breum et al., 1995
Sertraline and paroxetine Selective serotonin reuptake inhibitor	Peripheral	Improves glycemic control	Goodnick et al., 1997; Ueno et al., 2010
Mosapride or prucalopride 5-HT4 receptor agonist	Pancreatic tissue and islet cells of rats in vitro	Increases insulin release; elevates the serum insulin level accompanied by a decrease in blood glucose	Chen et al., 2016
5-HT4 receptor	Nucleus accumbens	Reduces the physiological drive to eat	Jean et al., 2007
Lorcaserin 5-HT2C receptor agonist	Peripheral	Loses weight and ameliorates glycemic parameters in prediabetes patients, and prevents progression to type 2 diabetes and accelerates reversion to normal blood glucose levels	Nesto et al., 2016
Lorcaserin 5-HT2C receptor agonist	Brainstem nucleus of solitary tract	Decreasing food intake when activated	D’Agostino et al., 2018
Glucagon-like peptide 1 receptor	Dorsal raphe Hypothalamus	Body weight reduction, anorexia, and fat mass loss; 5-HT turnover and expression of 5-HT2A and 5-HT2C receptors	Anderberg et al., 2017
M-chlorophenylpiperazine 5-HT2C receptor agonist	Peripheral	Ameliorates insulin sensitivity and glucose homeostasis	Berglund et al., 2013
Antagonists or genetic deletion of 5-HT2C receptors	Pro-opiomelanocortin neurons	Compromises glucose homeostasis	Berglund et al., 2013
Transcutaneous auricular vagus nerve stimulation (2/15 Hz, 2 mA)		Inhibits the progression of nociceptive hypersensitivity in Zucker diabetic fatty rats, this advantageous impact on nociceptive behavior is associated with an increase in 5-HT plasma levels and upregulated expression of the 5-HT1A receptor in the hypothalamus	Li et al., 2018
Duloxetine Inhibitor of serotonin and norepinephrine reuptake	Systemic or intrathecal injection	Alleviates tactile allodynia in diabetic rats	Mixcoatl-Zecuatl and Jolivalt, 2011