Ghrelin in neuroendocrine tumors

Vu, John P.; Wang, Hank S.; Germano, Patrizia M.; Pisegna, Joseph R.

doi:10.1016/j.peptides.2011.10.006

Cited by 14 publications

(14 citation statements)

References 75 publications

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“…Recently, several neuromediators have been suggested to play an important role in the regulation of appetite/satiety, feeding behavior and also in energy balance and metabolism (Wang, 2007; Greenwood, 2011; Vu, 2011). The ARC neurons, containing neurotransmitter peptides associated with appetite signals (Woods, 1998), communicate with each other and with higher brain centers through released PACAP, neuropeptide Y, agouti-related peptide neurons and melanocortin-releasing neurons (Delgado, 1996; Barsh, 2000).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP)

Larauche

Flores

et al. 2015

J Mol Neurosci

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Introduction Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide that belongs to the secretin-glucagon superfamily of peptides and has 68% homology with PACAP. VIP is abundantly expressed in the central and peripheral nervous system and in the gastrointestinal tract, where it exercises several physiological functions. Previously, it has been reported that VIP regulates feeding behavior centrally in different species of vertebrates such as goldfishes, chicken, and rodents. Additional studies are necessary to analyze the role of endogenous VIP on the regulation of appetite/satiety together with feeding behavior, metabolic hormone release, body mass composition and energy balance. Aims To elucidate the physiological pathways by which VIP regulates appetite/satiety, feeding behavior, metabolic hormones and body mass composition. Methods VIP deficient (VIP −/−) and age-matched wild-type (WT) littermates were weekly monitored from 5 to 22 weeks of age using a whole body composition EchoMRI analyzer. Food intake and feeding behavior were analyzed using the BioDAQ automated monitoring system. Plasma levels of metabolic hormones including active-ghrelin, GLP-1, leptin, PYY, pancreatic polypeptide (PP), adiponectin, and insulin were measured in fasting as well as in postprandial conditions. Results The genetic lack of VIP led to a significant reduction of body weight and fat mass and to an increase of lean mass as the mice aged. Additionally, VIP−/− mice had a disrupted pattern of circadian feeding behavior resulting in an abolished regular nocturnal/diurnal feeding. These changes were associated with an altered secretion of adiponectin, GLP-1, leptin, PYY and insulin in VIP−/− mice. Our data demonstrates that endogenous VIP is involved in the control of appetite/satiety, feeding behavior, body mass composition and in the secretion of six different key regulatory metabolic hormones. Conclusions Our data show that endogenous VIP is involved in the control of appetite/satiety, feeding behavior, body mass composition and in the secretion of six key regulatory metabolic hormones. VIP plays a key role in the regulation of body weight and mass composition phenotype by significantly enhancing body weight and fat mass accumulation. Therefore, VIP signaling is critical for the modulation of appetite/satiety and body mass phenotype and is suggested to be a target for future treatment of obesity.

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Section: Discussionmentioning

confidence: 99%

Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP)

Larauche

Flores

et al. 2015

J Mol Neurosci

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“…Desacyl ghrelin is considered the inactive form of ghrelin because it does not activate the ghrelin receptor (GHS-R1a) and does not induce the same endocrine effects of acyl ghrelin (19). Ghrelin has also been detected in the small intestine, hypothalamus, pituitary gland, pancreas, heart, and adipose tissue (11,19,25,55,57). Currently, the mechanisms regulating ghrelin secretion are not fully understood; however, peptide hormones such as oxytocin and dopamine have been reported to regulate in vitro ghrelin secretion (20).…”

Section: Discussionmentioning

confidence: 99%

PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin

Goyal

Luong

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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PM. PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin. Am J Physiol Gastrointest Liver Physiol 309: G816 -G825, 2015. First published September 3, 2015 doi:10.1152/ajpgi.00190.2015.-Pituitary adenylate cyclase-activating peptide (PACAP) is expressed within the gastroenteric system, where it has profound physiological effects. PACAP was shown to regulate food intake and thermogenesis centrally; however, PACAP peripheral regulation of appetite and feeding behavior is unknown. Therefore, we studied PACAP's effect on appetite and food intake control by analyzing feeding behavior and metabolic hormones in PAC1-deficient (PAC1Ϫ/Ϫ) and age-matched wild-type (WT) mice intraperitoneally injected with PACAP 1-38 or PACAP 1-27 before the dark phase of feeding. Food intake and feeding behavior were analyzed using the BioDAQ system. Active ghrelin, glucagon-like peptide-1 (GLP-1), leptin, peptide YY, pancreatic polypeptide, and insulin were measured following PACAP 1-38 administration in fasted WT mice. PACAP 1-38/PACAP1-27 injected into WT mice significantly decreased in a dose-dependent manner cumulative food intake and reduced bout and meal feeding parameters. Conversely, PACAP 1-38 injected into PAC1Ϫ/Ϫ mice failed to significantly change food intake. Importantly, PACAP1-38 reduced plasma levels of active ghrelin compared with vehicle in WT mice. In PAC1Ϫ/Ϫ mice, fasting levels of active ghrelin, GLP-1, insulin, and leptin and postprandial levels of active ghrelin and insulin were significantly altered compared with levels in WT mice. Therefore, PAC1 is a novel regulator of appetite/satiety. PACAP 1-38/PACAP1-27 significantly reduced appetite and food intake through PAC1. In PAC1Ϫ/Ϫ mice, the regulation of anorexigenic/orexigenic hormones was abolished, whereas active ghrelin remained elevated even postprandially. PACAP significantly reduced active ghrelin in fasting conditions. These results establish a role for PACAP via PAC1 in the peripheral regulation of appetite/satiety and suggest future studies to explore a therapeutic use of PACAP or PAC1 agonists for obesity treatment.pituitary adenylate cyclase-activating peptide; PAC1 receptor; appetite; ghrelin; GLP-1; leptin PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) was originally isolated from the ovine hypothalamus and is highly conserved among vertebrates (1). PACAP, because of its protein structure, particularly in the first 27 amino acids, belongs to the secretin-glucagon superfamily of hormones, which includes vasoactive intestinal peptide (VIP), gastric inhibitory peptide, glucagon-like peptide (GLP)-1 and GLP-2, growth hormone-releasing hormone, peptide histidine methionine, peptide histidine isoleucine, and exendins (34). PACAP exists in two variant forms: PACAP 1-27 and the COOHterminally extended form PACAP 1-38 that originates from the same precursor and stimulates adenylate cyclase activity in pituitary cells (23,35). PACAP functions through its P...

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“…Pancreatic polypeptide controls exocrine function of the pancreas [7] in response to hunger and satiety signaling from the gut-brain axis [8], and reduces gastric emptying [8]. Ghrelin contributes to gastrointestinal motility, regulation of appetite, response to hunger and starvation [3,[9][10][11][12][13][14][15][16][17][18][19], and inhibits nausea [18]. Gastrin controls release of histamine, a compound stimulating gastric cells to hydrochloric acid secretion, promotes cell migration, invasion, apoptosis, tubulogenesis and angiogenesis [20][21][22][23].…”

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confidence: 99%

Enterohormonal disturbances in colorectal cancer patients

Zygulska¹,

Furgała²,

Krzemieniecki³

et al. 2017

neo

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Gastrointestinal (GI) hormonal peptides play a role in the development of gastrointestinal malignancies, and their abnormal levels may contribute to dysmotility. The aim of this study was to analyze plasma concentrations of enterohormones (motilin, ghrelin, gastrin and pancreatic polypeptide) and to verify if their abnormal levels may contribute to the severity of dyspeptic symptoms in colorectal cancer patients. The study included 60 patients with colorectal malignancies (22 men and 38 women), among them 30 individuals with colon cancers (group A) and 30 subjects with rectal tumors (group B). Fasting plasma levels of pancreatic polypeptide (PP), motilin, gastrin and ghrelin were determined by means of ELISA. The results were compared with the respective parameters of healthy volunteers. Colon cancer patients presented with significantly lower concentrations of ghrelin than the subjects with rectal tumors and healthy controls (156.8±86.7 vs. 260.2±87.6 vs. 258.4±94.2 pg/ml, p=0.02), as well as with significantly higher levels of PP (265.5±66.3 vs. 154.1±54.6 vs. 148.3±64.3 pg/ml, p=0.005). Also the levels of motilin turned out to be lower in colon cancer patients than in the subjects with rectal malignancies and healthy controls. No statistically significant intergroups differences were found in plasma levels of gastrin (388.2±98.6 vs. 475.6±88.7 vs. 428.2±91.2 pg/ml, p>0.05). Epigastric bloating was the most frequent dyspeptic symptom, reported by 63.3% and 40% of patients with colon and rectal tumors, respectively. Our findings imply that colon cancer patients may present with abnormal plasma levels of enterohormones significantly more often than individuals with rectal malignancies. Dysmotility observed in colon cancer patients may result not only from anticancer surgery, but also from abnormal release of enterohormones, induced either by neoplastic process or by changes within the autonomic nervous system.

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Ghrelin in neuroendocrine tumors

Cited by 14 publications

References 75 publications

Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP)

Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP)

PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin

Enterohormonal disturbances in colorectal cancer patients

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