Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity

Oh, Chang‐Myung; Park, Soo Young; Kim, Hail

doi:10.4093/dmj.2016.40.2.89

Cited by 93 publications

(105 citation statements)

References 64 publications

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“…[165] Bromocriptine augments low hypothalamic dopamine levels and inhibits excessive sympathetic tone within the CNS, resulting in a reduction in post meal plasma glucose levels, due to enhanced suppression of hepatic glucose production [165]. Meanwhile, a peripheral serotonin inhibitor (LP-533401) has already been patented for treating diabetes and obesity [166], suggesting that in peripheral tissues, suppressing serotonin signaling might represent a new target for treating diabetes by improving insulin resistance [167, 168]. …”

Section: Therapeutic Interventionsmentioning

confidence: 99%

Cross-Talk Between Insulin Signaling and G Protein–Coupled Receptors

Shi²,

West

et al. 2017

Journal of Cardiovascular Pharmacology

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Summary Diabetes is a major risk factor for the development of heart failure. One of the hallmarks of diabetes is insulin resistance associated with hyperinsulinemia. The literature shows that insulin and adrenergic signaling is intimately linked to each other; however, whether and how insulin may modulate cardiac adrenergic signaling and cardiac function remains unknown. Notably, recent studies have revealed that insulin receptor and β2 adrenergic receptor (β2AR) forms a membrane complex in animal hearts, bringing together the direct contact between two receptor signaling systems, and forming an integrated and dynamic network. Moreover, insulin can drive cardiac adrenergic desensitization via PKA and GRK phosphorylation of the β2AR, which compromises adrenergic regulation of cardiac contractile function. In this review, we will explore the current state of knowledge linking insulin and GPCR signaling, especially βAR signaling in the heart, with emphasis on molecular insights regarding its role in diabetic cardiomyopathy (DCM).

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Section: Therapeutic Interventionsmentioning

confidence: 99%

Cross-Talk Between Insulin Signaling and G Protein–Coupled Receptors

Shi²,

West

et al. 2017

Journal of Cardiovascular Pharmacology

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“…However, serotonin plays different roles in different tissues by acting through different receptors. Thus, inhibition of serotonin synthesis in adipose tissue is a potentially beneficial strategy for anti-obesity treatment 1) .…”

Section: Resultsmentioning

confidence: 99%

“…Based on the newly identified roles of peripheral serotonin in energy homeostasis, serotonin can be considered as an energysaving hormone 1) . Modulating the peripheral serotonergic system may be a good strategy for anti-obesity treatment because it can decrease obesity and increase insulin sensitivity.…”

Section: Resultsmentioning

confidence: 99%

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Regulation of Systemic Energy Homeostasis by Peripheral Serotonin

Namkung¹,

Oh²,

Park³

et al. 2016

Journal of mucopolysaccharidosis and rare disease

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Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. Serotonin is among those traditional pharmacological targets for antiobesity treatment because central 5-HT functions as an anorexigenic neurotransmitter in the brain. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as antiobesity drugs. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Fat specific Tph1 knock-out (Tph1 FKO) mice exhibit similar phenotypes as mice with pharmacological inhibition of 5-HT synthesis, suggesting the localized effects of 5-HT in adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure in BAT and Htr2a KO mice exhibit the decreased lipid accumulation in WAT. These data suggest the clinical significance of the peripheral serotonergic system as a new therapeutic target for anti-obesity treatment.

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“…On the other hand, around 98% of the body's serotonin is found peripherally, where it functions as a peripheral hormone. It affects vasoconstriction, intestinal motility, primary hemostasis, liver repair, and the control of the T-cell-mediated immune system [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Energy Homeostasis by the Peripheral Serotonergic System

Watanabe

Rose²,

Kanayama

et al. 2017

Serotonin - A Chemical Messenger Between All Types of Living Cells

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Energy homeostasis is maintained by balancing energy intake and energy expenditure. In addition to the central nervous system, several hormones play a key role in energy homeostasis in the whole body. In particular, serotonin is regarded as one of the key regulators of energy homeostasis. Serotonin is unique in that it is able to act in both the brain as a neurotransmitter and the peripheral tissue as a gastrointestinal hormone. In the brain, serotonin is thought of as a pharmacological target for anti-obesity treatments because it greatly inhibits meal size and body weight gain. In contrast, serotonin in the periphery has not been targeted as a strategy for anti-obesity treatment, even though almost all of the serotonin produced in the body is produced in the peripheral tissue. Recently, the peripheral serotonergic signal has been shown to regulate glucose and lipid metabolism through autocrine and paracrine signals in energy homeostasis-related tissues, including the pancreatic β cell, liver, white adipose tissue, brown adipose tissue, and skeletal muscle. Thus, it is possible that the serotonergic system in the peripheral tissue is a new therapeutic target for metabolic disease, including obesity and diabetes. Here, we summarize the role of peripheral serotonin in the regulation of energy homeostasis.

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Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity

Cited by 93 publications

References 64 publications

Cross-Talk Between Insulin Signaling and G Protein–Coupled Receptors

Cross-Talk Between Insulin Signaling and G Protein–Coupled Receptors

Regulation of Systemic Energy Homeostasis by Peripheral Serotonin

Energy Homeostasis by the Peripheral Serotonergic System

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