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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcription factor regulatory factor X (RFX)-3 regulates the expression of genes required for the growth and function of cilia. We show here that mouse RFX3 is expressed in developing and mature pancreatic endocrine cells during embryogenesis and in adults. RFX3 expression already is evident in early Ngn3-positive progenitors and is maintained in all major pancreatic endocrine cell lineages throughout their development. Primary cilia of hitherto unknown function present on these cells consequently are reduced in number and severely stunted in Rfx3(-/-) mice. This ciliary abnormality is associated with a developmental defect leading to a uniquely altered cellular composition of the islets of Langerhans. Just before birth, Rfx3(-/-) islets contain considerably less insulin-, glucagon-, and ghrelin-producing cells, whereas pancreatic polypeptide-positive cells are markedly increased in number. In adult mice, the defect leads to small and disorganized islets, reduced insulin production, and impaired glucose tolerance. These findings suggest that RFX3 participates in the mechanisms that govern pancreatic endocrine cell differentiation and that the presence of primary cilia on islet cells may play a key role in this process.
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PMID:Novel function of the ciliogenic transcription factor RFX3 in development of the endocrine pancreas. 1722 40

The purpose of this study was to investigate the pathophysiologic change of ghrelin in gastric and colorectal cancer patients, especially in those with cachexia. Fifty-eight gastric cancer patients, 20 colorectal cancer patients, and 24 healthy control individuals were included in this study. Thirty-one patients were defined as cachectic, based on the percentage of weight loss versus the previous normal weight. The remaining 47 patients were defined as noncachectic. Peripheral hormones, including ghrelin, insulin, leptin, growth hormone, glucagon, and cortisol, and body composition parameters were measured. Plasma ghrelin levels did not increase significantly in cachectic gastric (p = 0.352) or colorectal (p = 0.871) cancer patients as compared with controls and were not correlated with nutrition status and other hormones. The location of gastric cancer (proximal vs. distal) had no influence on ghrelin levels (p = 0.966). These findings suggest that gastric and colorectal cancers may have their special effects on the production of ghrelin. Gastric or colorectal cancer cachexia may be partly due to the lack of increase in ghrelin, which makes exogenous ghrelin therapy feasible in this setting.
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PMID:Circulating ghrelin in patients with gastric or colorectal cancer. 1724 26

Ghrelin is a 28 amino acid stomach peptide, derived from proghrelin(1-94), that stimulates GH release, appetite and adipose deposition. Recently, a peptide derived from proghrelin(53-75) -- also known as obestatin -- has been reported to be a physiological antagonist of ghrelin in the rat. Using four specific RIAs, we provide the first characterisation of proghrelin(1-94) peptides in human plasma, their modulation by metabolic manipulation and their distribution in mammalian tissues. ghrelin(1-28) immunoreactivity (IR) in human plasma and rat plasma/stomach consisted of major des-octanoyl and minor octanoylated forms, as determined by HPLC/RIA. Human plasma ghrelin(1-28) IR was significantly suppressed by food intake, oral glucose and 1 mg s.c. glucagon administration. ghrelin(1-28) IR and proghrelin(29-94) IR peptide distributions in the rat indicated that the stomach and gastrointestinal tract contain the highest amounts of the peptides. Human and rat plasma and rat stomach extracts contained a major IR peak of proghrelin(29-94)-like peptide as determined by HPLC/RIA, whereas no obestatin IR was observed. Human plasma proghrelin(29-94)-like IR positively correlated with ghrelin(1-28) IR, was significantly suppressed by food intake and oral glucose and shared with ghrelin(1-28) IR a negative correlation with body mass index. We found no evidence for the existence of obestatin as a unique, endogenous peptide. Rather, our data suggest that circulating and stored peptides derived from the carboxyl terminal of proghrelin (C-ghrelin) are consistent in length with proghrelin(29-94) and respond to metabolic manipulation, at least in man, in similar fashion to ghrelin(1-28).
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PMID:Characterisation of proghrelin peptides in mammalian tissue and plasma. 1728 31

Several circulating or urinary tumour markers can be used for the diagnosis and follow-up of functioning and clinically non-functioning neuroendocrine tumours of the pancreatic islet cells and intestinal tract. Among the specific tumour markers are serotonin and its metabolites--e.g. 5-hydroxyindoleacetic acid (5-HIAA)--in carcinoid tumours and the carcinoid syndrome, insulin and its precursors or breakdown products in insulinoma, and gastrin in gastrinoma. Plasma vasointestinal polypeptide (VIP) determinations have been used in the diagnosis of VIPoma, plasma glucagon for glucagonoma, and serum somatostatin for somatostatinoma. Among the tumour-non-specific markers are: chromogranins, neuron-specific enolase (NSE), alpha-subunits of the glycoprotein hormones, catecholamines, pancreatic polypeptide (PP), ghrelin and adrenomedullin.
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PMID:Biochemistry of neuroendocrine tumours. 1738 64

The master clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus regulates circadian rhythms in mammals. The clock is an intracellular, transcriptional mechanism sharing the same molecular components in SCN neurons and in peripheral cells, such as the liver, intestine, and retina. The circadian clock controls food processing and energy homeostasis by regulating the expression and/or activity of enzymes involved in cholesterol, amino acid, lipid, glycogen, and glucose metabolism. In addition, many hormones involved in metabolism, such as insulin, glucagon, adiponectin, corticosterone, leptin, and ghrelin, exhibit circadian oscillation. Furthermore, disruption of circadian rhythms is involved in the development of cancer, metabolic syndrome, and obesity. Metabolism and food intake also feed back to influence the biological clock. Calorie restriction (CR) entrains the SCN clock, whereas timed meals entrain peripheral oscillators. Furthermore, the cellular redox state, dictated by food metabolism, and several nutrients, such as glucose, ethanol, adenosine, caffeine, thiamine, and retinoic acid, can phase-shift circadian rhythms. In conclusion, there is a large body of evidence that links feeding regimens, food components, and the biological clock.
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PMID:The relationship between nutrition and circadian rhythms in mammals. 1745 93

The present study was performed to evaluate the role of glucagon in the regulation of ghrelin secretion from the rat stomach. mRNA for ghrelin and glucagon receptor was expressed predominantly in the lower body and pylorus of stomach, but little or not in the upper body and cardia. Ghrelin- and glucagon receptor-immunoreactive cells were detected in lamina propria mucosae of stomach and some cells expressed both. Intravenous administration of glucagon caused transient increases in both acyl- and desacyl-ghrelin levels in the gastric vein within 10 min, which was followed by gradual increases in desacyl-ghrelin levels until 60 min. Steady state levels of ghrelin mRNA in the stomach were increased by 1.9-fold 20 min after glucagon administration, but not at 5 or 120 min. These results suggest that glucagon stimulates acute release of both forms of ghrelin and thereafter upregulates synthesis and release of desacyl-ghrelin in the rat stomach.
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PMID:Glucagon receptor expression and glucagon stimulation of ghrelin secretion in rat stomach. 1746 98

This study investigated the acute effects of exercise on the postprandial levels of appetite-related hormones and metabolites, energy intake (EI) and subjective measures of appetite. Ghrelin, polypeptide YY (PYY), glucagon-like peptide-1 (GLP-1) and pancreatic polypeptide (PP) were measured in the fasting state and postprandially in 12 healthy, normal-weight volunteers (six males and six females) using a randomised crossover design. One hour after a standardised breakfast, subjects either cycled for 60 min at 65% of their maximal heart rate or rested. Subjective appetite was assessed throughout the study using visual analogue scales and subsequent EI at a buffet meal was measured at the end (3-h post-breakfast and 1-h post-exercise). Exercise significantly increased mean PYY, GLP-1 and PP levels, and this effect was maintained during the post-exercise period for GLP-1 and PP. No significant effect of exercise was observed on postprandial levels of ghrelin. During the exercise period, hunger scores were significantly decreased; however, this effect disappeared in the post-exercise period. Exercise significantly increased subsequent absolute EI, but produced a significant decrease in relative EI after accounting for the energy expended during exercise. Hunger scores and PYY, GLP-1 and PP levels showed an inverse temporal pattern during the 1-h exercise/control intervention. In conclusion, acute exercise, of moderate intensity, temporarily decreased hunger sensations and was able to produce a short-term negative energy balance. This impact on appetite and subsequent energy homeostasis was not explained by changes in postprandial levels of ghrelin; however, 'exercise-induced anorexia' may potentially be linked to increased PYY, GLP-1 and PP levels.
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PMID:Effects of exercise on gut peptides, energy intake and appetite. 1747 May 16

Traditionally there has been a tendency to focus on peripheral "bottom-up" feeding-related signals and their resulting downstream actions on hypothalamic centers when studying the feeding behaviour of animals. A problem with this hierarchal approach emerges especially with respect to acquiring a human model attempting to explain what is ultimately a distributed control of feeding and energy balance. This review focuses on illuminating the means by which we have come to understand the complexities of feeding, and takes the next step in an attempt to propose a distinctive top-down view of this composite behaviour. It is argued that in evolutionary terms humans demonstrate behaviours unique to all species as represented by an expanded forebrain and the resultant psychological "non-homeostatic" mediators of feeding. Emphasis is placed on a distributionist "two-tier" model, arguing that traditional short-term (cholescystokinin, ghrelin, peptide YY, glucagon-like peptide 1, etc.) and long-term (insulin and leptin) feeding signals may be actively suppressed by the nested nuclei and projections of cortical-limbic brain areas. It is the motivational state (dependent on depletion-repletion signals of hunger and satiety) that in turn has the capability to modulate how rewarding or how palatable a food item may be perceived; thus, both sides of the two-tiered model of feeding behaviour are complimentary and interdependent all at once. In the end, this paper is both commentary and critical review. This synthesis purports that as evolutionary processes spawned consciousness, the psychology of hunger and the present-day discordance of gene-environment interaction forever changed the feeding behaviour of Homo sapiens.
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PMID:Getting to the bottom of feeding behaviour: who's on top? 1748 58

Obesity is a major public health problem associated with morbidity and mortality and continues to increase worldwide. This review focuses on the regions of the brain that are important in appetite regulation and the circulating factors implicated in the control of food intake. The hypothalamus is critical in the regulation of food intake containing neural circuits, which produce a number of peptides that influence food intake. The arcuate nucleus of the hypothalamus produces both orexigenic peptides (agouti-related protein and neuropeptide Y) and anorectic peptides (alpha-melanocyte-stimulating hormone and cocaine- and amphetamine-related transcript). The lateral hypothalamus produces the orexigenic peptides (melanin-concentrating hormone and orexins). Other hypothalamic factors recently implicated in appetite regulation include the endocannabinoids, brain-derived neurotrophic factor, nesfatin-1, AMP-activated protein kinase, mammalian target of rapamycin protein, and protein tyrosine phosphatase. Circulating factors that affect food intake mediate their effects by signaling to the hypothalamus and/or brainstem. A number of circulating factors are produced by peripheral organs, for example, leptin by adipose tissue, insulin and pancreatic polypeptide by the pancreas, gut hormones (e.g., ghrelin, obestatin, glucagon-like peptide-1, oxyntomodulin, peptide YY), and triiodothyronine by the thyroid gland. Circulating carbohydrates, lipids, and amino acids also affect appetite regulation. Knowledge regarding appetite regulation has vastly expanded in recent years providing targets for antiobesity drug design.
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PMID:Appetite regulation: an overview. 1754 73

Ghrelin is produced by A-like cells (ghrelin cells) in the mucosa of the acid-producing part of the stomach. The mobilization of ghrelin is stimulated by nutritional deficiency and suppressed by nutritional abundance. In an attempt to identify neurotransmitters and regulatory peptides that may contribute to the physiological, nutrient-related regulation of ghrelin secretion, we challenged the ghrelin cells in situ with a wide variety of candidate messengers, including known neurotransmitters (e.g. acetylcholine, catecholamines), candidate neurotransmitters (e.g. neuropeptides), local tissue hormones (e.g. serotonin, histamine, bradykinin, endothelin), circulating gut hormones (e.g. gastrin, CCK, GIP, neurotensin, PYY, secretin) and other circulating hormones/regulatory peptides (e.g. calcitonin, glucagon, insulin, PTH). Microdialysis probes were placed in the submucosa of the acid-producing part of the rat stomach. Three days later, the putative messenger compounds were administered via the microdialysis probe (reverse microdialysis) at a screening dose of 0.1 mmol l(-1) for regulatory peptides and 0.1 and 1 mmol l(-1) for amines and amino acids. The rats were awake during the experiments. The resulting microdialysate ghrelin concentration was monitored continuously for 3 h (radioimmunoassay), thereby revealing stimulators or inhibitors of ghrelin secretion. Dose-response curves were constructed for each candidate messenger that significantly (p<0.05) affected ghrelin mobilization at the screening dose. Peptides that showed a (non-significant) tendency to affect ghrelin release at the screening dose were also given at a dose of 0.3 or 1 mmol l(-1). Adrenaline, noradrenaline, endothelin and secretin stimulated ghrelin release, while somatostatin and GRP inhibited. Whether these agents act directly or indirectly on the ghrelin cells remains to be investigated. All other candidate messengers were without measurable effects, including acetylcholine, serotonin, histamine, GABA, aspartic acid, glutamic acid, glycine, VIP, PACAP, CGRP, substance P, NPY, PYY, PP, gastrin, CCK, GIP, insulin, glucagon, GLP and glucose.
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PMID:Secretion of ghrelin from rat stomach ghrelin cells in response to local microinfusion of candidate messenger compounds: a microdialysis study. 1757 35


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