Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation

Moon, Joon Ho; Kim, Yeong Gi; Kim, Kyuho; Osonoi, Sho; Wang, Shuang; Saunders, Diane; Wang, Juehu; Yang, Katherine; Kim, Hyeongseok; Lee, Junguee; Jeong, Ji‐Seon; Banerjee, Ronadip R.; Kim, Seung K.; Wu, Yingjie; Mizukami, Hiroki; Powers, Alvin C.; German, Michael S.; Kim, Hail

doi:10.2337/db19-0546

Cited by 42 publications

(47 citation statements)

References 40 publications

(42 reference statements)

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“…At intestinal levels, NPY acts in autocrine or paracrine manner to regulate all aspects of nutrient homeostasis including satiety, mechanical and chemical digestion, nutrient absorption, storage and utilization [49]. In addition, we observed NPY immunoreactivity in glucagon cells of pancreatic islets, further confirmed by immunofluorescence experiments which excluded co-presence of NPY with 5-HT, known to be marker of insulin cells [50,51]. 5-HT is synthesized by β-cells and promotes their functions [52], regulating insulin secretion as local autocrine/paracrine signal [53] and inhibiting glucan secretion in paracrine manner [50].…”

Section: Discussionsupporting

confidence: 75%

Distinct Pattern of NPY in Gastro–Entero–Pancreatic System of Goat Kids Fed with a New Standardized Red Orange and Lemon Extract (RLE)

Felice

Giaquinto

Damiano

et al. 2021

Animals

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The use of natural compounds as feed additive is also increasing in farm animals, thanks to the beneficial effect on both animals and consumers health. Here, we questioned whether natural extracts, such as red orange and lemon extract (RLE) rich in flavanones, anthocyanins, and other polyphenols, used as feed additives could display an effect on the neuropeptide Y (NPY) in the gastro–entero–pancreatic tract of goat kids. NPY is one of the most abundant neuropeptides in mammals, known for its orexigenic role although it is involved in many central and peripheral functions. We carried out immunohistochemical analyses on samples of abomasum, duodenum and pancreas collected from two experimental groups: one fed with standard diet and one with standard diet + RLE. For the first time we document NPY distribution in the abomasum, duodenum and pancreas of goats and observe the highest number of NPY positive cells in neuroendocrine cells of duodenum. Remarkably, upon RLE feed supplementation, NPY immunoreactive cells increased significantly in abomasal epithelium and pancreatic islets but not in duodenum, likely due to pH variation of abomasum and duodenum. Our observations represent a baseline for future studies on the interaction between neuropeptides and polyphenols, used as feed additive.

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Section: Discussionsupporting

confidence: 75%

Distinct Pattern of NPY in Gastro–Entero–Pancreatic System of Goat Kids Fed with a New Standardized Red Orange and Lemon Extract (RLE)

Felice

Giaquinto

Damiano

et al. 2021

Animals

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“…During the perinatal period, disruption of Tph1 in β-cells resulted in their loss of 5-HT production, reducing perinatal β-cell proliferation and β-cell mass by more than 50%. This reduction in β-cell mass impaired glucose tolerance in adulthood and increased susceptibility to diabetes in response to metabolic stress (Moon et al 2020b). Furthermore, β-cell-specific Htr2b knock-out mice phenocopied β-cell-specific Tph1 knock-out mice, suggesting that HTR2B acts downstream of 5-HT in regulating perinatal β-cell proliferation.…”

Section: Metabolic Roles Of 5-ht In Pancreatic β-Cellsmentioning

confidence: 99%

Serotonergic regulation of energy metabolism in peripheral tissues

Choi

Moon

Kim

2020

Journal of Endocrinology

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Serotonin is a biogenic amine synthesized from the essential amino acid tryptophan. Because serotonin cannot cross the blood-brain barrier, it functions differently in neuronal and non-neuronal tissues. In the CNS, serotonin regulates mood, behavior, appetite, and energy expenditure. Although most serotonin in the body is synthesized at the periphery, its biological roles have not been well elucidated. Older studies using chemical agonists and antagonists yielded conflicting results, because the complexity of serotonin receptors and the low selectivity of agonists and antagonists were not known. Several recent studies using specific knock-out of serotonin receptors have been performed to assess the role of peripheral serotonin in regulating energy metabolism. This review discusses (1) the tissue-specific roles of peripheral serotonin in regulating energy metabolism, (2) the mechanism by which dysfunctional peripheral serotonin signaling can progress to metabolic diseases, and (3) how peripheral serotonin signaling could be a therapeutic target for metabolic diseases.

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“…In human islets, 5-HT serves a paracrine role by inhibiting glucagon release from alpha cells [39,40]. In mice, 5-HT production is normally low, but a notable increase in the local production of 5-HT by mouse beta cells is responsible for the robust increase in beta cell mass during pregnancy [41] and drives the perinatal expansion of beta cell mass that determines adult beta cell mass [42]. GABA is synthesised by GAD expressed by beta cells (in fact, GAD is an autoantigen in type 1 diabetes).…”

Section: Autocrine Actions Of Beta Cell-produced Neurotransmittersmentioning

confidence: 99%

Paracrine regulation of insulin secretion

Huising

2020

Diabetologia

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Pancreatic beta cells are the only cell type in our body capable of producing and secreting insulin to instruct the insulin-sensitive cells and tissues of our bodies to absorb nutrients after a meal. Accurate control of insulin release is of critical importance; too little insulin leads to diabetes, while an excess of insulin can cause potentially fatal hypoglycaemia. Yet, the pancreas of most people will control insulin secretion safely and effectively over decades and in response to glucose excursions driven by tens of thousands of meals. Because we only become aware of the important contributions of the pancreas when it fails to maintain glucose homeostasis, it is easy to forget just how well insulin release from a healthy pancreas is matched to insulin need to ensure stable blood glucose levels. Beta cells achieve this feat by extensive crosstalk with the rest of the endocrine cell types in the islet, notably the glucagon-producing alpha cells and somatostatin-producing delta cells. Here I will review the important paracrine contributions that each of these cells makes to the stimulation and subsequent inhibition of insulin release in response to a transient nutrient stimulation, and make the case that a breakdown of this local crosstalk contributes to the pathophysiology of diabetes.

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Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation

Cited by 42 publications

References 40 publications

Distinct Pattern of NPY in Gastro–Entero–Pancreatic System of Goat Kids Fed with a New Standardized Red Orange and Lemon Extract (RLE)

Distinct Pattern of NPY in Gastro–Entero–Pancreatic System of Goat Kids Fed with a New Standardized Red Orange and Lemon Extract (RLE)

Serotonergic regulation of energy metabolism in peripheral tissues

Paracrine regulation of insulin secretion

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