GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis

Hong, Lan; Vassileva, Galya; Corona, Aaron; Liu, Li; Baker, Hana E.; Головко, Андрей; Abbondanzo, Susan J.; Hu, Weiwen; Yang, Shi Yu; Ning, Yun; Vecchio, Robert A. Del; Poulet, Frederique M.; Laverty, Maureen; Gustafson, Eric L.; Hedrick, Joseph A.; Kowalski, Timothy J.

doi:10.1677/joe-08-0453

Cited by 140 publications

(125 citation statements)

References 21 publications

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“…In order to evaluate this idea more fully, the distribution of GPR119 expression was examined in mammalian tissues by a number of authors and it was rapidly established that both the endocrine pancreas and certain cells of the GI tract express the receptor [87][88][89][90][91][92]. It is also possible that GPR119 may be expressed in some brain regions [93].…”

Section: Gpr119mentioning

confidence: 99%

“…Indeed, a recent study has revealed that, in mice deficient in GPR119, administration of OEA still exerts a powerful hypophagic response, suggesting that GPR119 is not absolutely required for this effect [113]. Nevertheless, GPR119 remains a potentially important pharmacological target for the improvement of glucose-induced insulin secretion in patients in whom this response is impaired.…”

Section: Ligands Of Gpr119mentioning

confidence: 99%

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G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

Morgan¹,

Dhayal²

2009

Biochemical Pharmacology

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It is increasingly clear that some of the effects of both free and derivatised long chain fatty acids in pancreatic beta-cells are mediated by a group of G-protein coupled receptors. Some of these display close structural homology while others are more divergent. This Commentary reviews the expression and functional roles of three such molecules, GPR40, GPR119 and GPR120. GPR40 is the best characterised of this group and appears to mediate the acute stimulatory effects of long chain fatty acids on insulin secretion. GPR40 has also been proposed as a potential mediator of fatty acid toxicity but this is more controversial. GPR119 is also involved in stimulation of insulin secretion and responds primarily to ethanolamine derivatives of long chain fatty acids and also to some lysophospholipids rather than to free fatty acids. It may represent a useful target for the development of new insulin secretagogues aimed to enhance insulin release in patients with type 2 diabetes. GPR120 is the most enigmatic of the lipid responsive cell-surface receptors and its function remains to be established. It has been proposed to play a cytoprotective role in certain other cell types but it is unclear whether it fulfils a similar function in beta-cells.

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Section: Gpr119mentioning

confidence: 99%

Section: Ligands Of Gpr119mentioning

confidence: 99%

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

Morgan¹,

Dhayal²

2009

Biochemical Pharmacology

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“…GPR119 is present in L-and K-cells [43,44] and participates in GLP-1, PYY, and GIP release [66]. Ingestion of nutrients stimulates the release of OEA in the small intestine, which can induce the release of GLP-1 [67].…”

Section: Gastrointestinal Lipid Sensingmentioning

confidence: 99%

Neuroendocrine control of satiation

Asarian¹,

Bächler

2014

Hormone Molecular Biology and Clinical Investigation

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Abstract:Eating is a simple behavior with complex functions. The unconscious neuroendocrine process that stops eating and brings a meal to its end is called satiation. Energy homeostasis is mediated accomplished through the control of meal size via satiation. It involves neural integrations of phasic negative-feedback signals related to ingested food and tonic signals, such as those related to adipose tissue mass. Energy homeostasis is accomplished through adjustments in meal size brought about by changes in these satiation signals. The best understood meal-derived satiation signals arise from gastrointestinal nutrient sensing. Gastrointestinal hormones secreted during the meal, including cholecystokinin, glucagon-like peptide 1, and PYY, mediate most of these. Other physiological signals arise from activation of metabolic-sensing neurons, mainly in the hypothalamus and caudal brainstem. We review both classes of satiation signal and their integration in the brain, including their processing by melanocortin, neuropeptide Y/agouti-related peptide, serotonin, noradrenaline, and oxytocin neurons. Our review is not comprehensive; rather, we discuss only what we consider the best-understood mechanisms of satiation, with a special focus on normally operating physiological mechanisms.

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“…Arena Pharmaceuticals has recently reported that stimulation of GPR119 under hyperglycemic conditions leads to a dual nutrient dependent insulinotropic and incretinotropic effect to maintain glucose homeostasis [152][153][154]. Unlike receptors for GLP-1 and other peptides that mediate enhanced glucose-dependent insulin release, GPR119 has proven amenable to the development of potent, orally active, small-molecule agonists [158].…”

Section: G Protein-coupled Receptor 119 (Gpr119) Is Expressed In Insumentioning

confidence: 99%

Diabetes Mellitus: New Challenges and Innovative Therapies

Sena¹,

Bento²,

Pereira³

et al. 2013

New Strategies to Advance Pre/Diabetes Care: Integrative Approach by PPPM

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Diabetes mellitus is a widespread disease prevalence and incidence of which increases worldwide. The introduction of insulin therapy represented a major breakthrough in type 1 diabetes; however, frequent hyper-and hypoglycemia seriously affects the quality of life of these patients. New therapeutic approaches, such as whole pancreas transplant or pancreatic islet transplant, stem cell, gene therapy and islets encapsulation are discussed in this review. Regarding type 2 diabetes, therapy has been based on drugs that stimulate insulin secretion (sulphonylureas and rapid-acting secretagogues), reduce hepatic glucose production (biguanides), delay digestion and absorption of intestinal carbohydrate (alpha-glucosidase inhibitors) or improve insulin action (thiazolidinediones). This review is also focused on the newer therapeutically approaches such as incretin-based therapies, bariatric surgery, stem cells and other emerging therapies that promise to further extend the options available. Gene-based therapies are among the most promising emerging alternatives to conventional treatments. Some of these therapies rely on genetic modification of non-differentiated cells to express pancreatic endocrine developmental factors, promoting differentiation of nonendocrine cells into β-cells, enabling synthesis and secretion of insulin in a glucose-regulated manner. Alternative therapies based on gene silencing using vector systems to deliver interference RNA to cells (i.e. against VEGF in diabetic retinopathy) are also a promising therapeutic option for the treatment of several diabetic complications. In conclusion, treatment of diabetes faces now a new era that is characterized by a variety of innovative therapeutic approaches that will improve quality-life and allow personalized therapyplanning in the near future.

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GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis

Cited by 140 publications

References 21 publications

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

Neuroendocrine control of satiation

Diabetes Mellitus: New Challenges and Innovative Therapies

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