The aromatic amino acid sensor GPR142 controls metabolism through balanced regulation of pancreatic and gut hormones

Rudenko, Olga; Shang, Jin; Munk, Alexander; Ekberg, Jeppe H.; Petersen, Natalia; Engelstoft, Maja S.; Egerod, Kristoffer L.; Hjorth, Siv A.; Wu, Margaret; Feng, Yue; Zhou, Yunping; Mokrosiński, Jacek; Thams, Peter; Reimann, Frank; Gribble, Fiona M.; Rehfeld, Jens F.; Holst, Jens J.; Treebak, Jonas T.; Howard, Andrew D.; Schwartz, Thue W.

doi:10.1016/j.molmet.2018.10.012

Cited by 49 publications

(42 citation statements)

References 45 publications

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“…Oligopeptide stimulation of GLP-1 release is impaired upon treatment of L-cell cultures with a CaSR antagonist and is ameliorated in mice deficient for the peptide transporter 1 (PEPT1) [302]. Aromatic amino acids such as phenylalanine, however, also interact with GPR142 [315].…”

Section: Regulation Of Glp-1 Secretionmentioning

confidence: 99%

Glucagon-like peptide 1 (GLP-1)

Müller¹,

Finan²,

Bloom³

et al. 2019

Molecular Metabolism

1,141

861

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BackgroundThe glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity.Scope of reviewIn this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases.Major conclusionsSince its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders

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Section: Regulation Of Glp-1 Secretionmentioning

confidence: 99%

Glucagon-like peptide 1 (GLP-1)

Müller¹,

Finan²,

Bloom³

et al. 2019

Molecular Metabolism

1,141

861

View full text Add to dashboard Cite

show abstract

“…2012). GPR142 is implicated in tryptophan, but not protein-induced GIP and GLP-1 release (Rudenko et al . 2019).…”

Section: Mechanisms Controlling Gut Hormone Secretionmentioning

confidence: 99%

Mechanisms controlling hormone secretion in human gut and its relevance to metabolism

Martin

Sun

Keating

2020

Journal of Endocrinology

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The homoeostatic regulation of metabolism is highly complex and involves multiple inputs from both the nervous and endocrine systems. The gut is the largest endocrine organ in our body and synthesises and secretes over 20 different hormones from enteroendocrine cells that are dispersed throughout the gut epithelium. These hormones include GLP-1, PYY, GIP, serotonin, and CCK, each of which play pivotal roles in maintaining energy balance and glucose homeostasis. Some are now the basis of several clinically used glucose-lowering and weight loss therapies. The environment in which these enteroendocrine cells exist is also complex, as they are exposed to numerous physiological inputs including ingested nutrients, circulating factors and metabolites produced from neighbouring gut microbiome. In this review, we examine the diverse means by which gut-derived hormones carry out their metabolic functions through their interactions with different metabolically important organs including the liver, pancreas, adipose tissue and brain. Furthermore, we discuss how nutrients and microbial metabolites affect gut hormone secretion and the mechanisms underlying these interactions.

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“…G-protein-coupled receptor 142 (GPR142) is a Gq-coupled GPCR, which is highly and almost exclusively expressed in pancreatic β, α, and enteroendocrine cells [127]. Although with a lower expression, GPR142 has also been detected in stomach, the duodenum, the ileum, and the jejunum [128].…”

Section: G-protein-coupled Receptor 142 (Gpr142)mentioning

confidence: 99%

Metabolite Sensing GPCRs: Promising Therapeutic Targets for Cancer Treatment?

Cosín-Roger

Ortiz-Masiá

Barrachina

et al. 2020

Cells

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G-protein-coupled receptors constitute the most diverse and largest receptor family in the human genome, with approximately 800 different members identified. Given the well-known metabolic alterations in cancer development, we will focus specifically in the 19 G-protein-coupled receptors (GPCRs), which can be selectively activated by metabolites. These metabolite sensing GPCRs control crucial processes, such as cell proliferation, differentiation, migration, and survival after their activation. In the present review, we will describe the main functions of these metabolite sensing GPCRs and shed light on the benefits of their potential use as possible pharmacological targets for cancer treatment.

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The aromatic amino acid sensor GPR142 controls metabolism through balanced regulation of pancreatic and gut hormones

Cited by 49 publications

References 45 publications

Glucagon-like peptide 1 (GLP-1)

Glucagon-like peptide 1 (GLP-1)

Mechanisms controlling hormone secretion in human gut and its relevance to metabolism

Metabolite Sensing GPCRs: Promising Therapeutic Targets for Cancer Treatment?

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