Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ghrelin, a novel growth hormone-releasing peptide isolated from human and rat stomach, is a 28-amino acid peptide with a posttranslational acylation modification that is indispensable for stimulating growth hormone secretion by increasing intracellular Ca(2+) concentration. It also functions in the regulation of feeding behavior, energy metabolism, and gastric acid secretion and motility. Using two different antibodies against the NH(2)- and COOH-terminal regions of ghrelin, we studied its localization in human and rat pancreas by immunohistochemistry. Ghrelin-immunoreactive cells were identified at the periphery of pancreatic islets in both species. Ghrelin co-localized exclusively with glucagon in rat islets, indicating that it is produced in alpha-cells. We identified ghrelin and des-acyl ghrelin in the rat pancreas using reverse-phase high-performance liquid chromatography combined with two radioimmunoassays. We also detected mRNA encoding ghrelin and its receptor in the rat pancreatic islets. Ghrelin increased the cytosolic free Ca(2+) concentration in beta-cells and stimulated insulin secretion when it was added to isolated rat pancreatic islets. These findings indicate that ghrelin may regulate islet function in an endocrine and/or paracrine manner.
 ...
PMID:Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. 1175 31

Ghrelin is a new gastric peptide involved in food intake control and growth hormone release. We aimed to assess its cell localisation in man during adult and fetal life and to clarify present interspecies inconsistencies of gastric endocrine cell types. A specific serum generated against amino acids 13-28 of ghrelin was tested on fetal and adult gastric mucosa and compared with ghrelin in situ hybridisation. Immunogold electron microscopy was performed on normal human, rat and dog adult stomach. Ghrelin cells were detected in developing gut, pancreas and lung from gestational week 10 and in adult human, rat and dog gastric mucosa. By immunogold electron microscopy, gastric ghrelin cells showed distinctive morphology and hormone reactivity in respect to histamine enterochromaffin-like, somatostatin D, glucagon A or serotonin enterochromaffin cells. Ghrelin cells were characterised by round, compact, electron-dense secretory granules of P/D(1) type in man (mean diameter 147+/-30 nm), A-like type in the rat (183+/-37 nm) and X type in the dog (273+/-49 nm). It is concluded that, ghrelin is produced by well-defined cell types, which in the past had been labelled differently in various mammals mostly because of the different size of their secretory granule. In man ghrelin cells develop during early fetal life.
 ...
PMID:Characterisation of gastric ghrelin cells in man and other mammals: studies in adult and fetal tissues. 1210 1

Ghrelin is a novel enteric hormone that stimulates growth hormone (GH), ACTH, and epinephrine; augments plasma glucose; and increases food intake by inducing the feeling of hunger. These characteristics make ghrelin a potential counterregulatory hormone. At present, it is not known whether ghrelin increases in response to insulin-induced hypoglycemia. To answer this question, we compared plasma ghrelin concentrations after a short-term insulin infusion that was allowed or not (euglycemic clamp) to cause hypoglycemia (2.7 +/- 0.2 mmol/l at 30 min) in five healthy volunteers. In both studies, plasma ghrelin concentrations decreased (P < 0.01) after insulin infusion (hypoglycemia by 14%, euglycemia by 22%), reached a nadir at 30 min, and returned to baseline at 60 min, without differences between the hypoglycemia and the euglycemia studies. Glucagon, cortisol, and GH increased in response to hypoglycemia despite the decreased ghrelin. There was a strong correlation (R(2) = 0.91, P < 0.002) between the insulin sensitivity of the subjects and the percentage suppression of ghrelin from baseline. These data demonstrate that ghrelin is not required for the hormonal defenses against insulin-induced hypoglycemia and that insulin can suppress ghrelin levels in healthy humans. These results raise the possibility that postprandial hyperinsulinemia is responsible for the reduction of plasma ghrelin that occurs during meal intake.
 ...
PMID:Ghrelin is not necessary for adequate hormonal counterregulation of insulin-induced hypoglycemia. 1235 26

Ghrelin possesses endocrine and non-endocrine actions mediated by the GH Secretagogue (GHS)-Receptors (GHS-R). The regulation of ghrelin secretion is still largely unknown. Somatostatin (SRIF) modulates central and gastroenteropancreatic hormonal secretions and functions. SRIF actions are partially shared by cortistatin (CST), a natural SRIF analogue, that binds all SRIF receptors and also GHS-R. Herein, we studied the effects of SRIF-14 or CST-14 (2.0 micro g/kg/h i.v. over 120 min) and of placebo on ghrelin, GH, insulin, glucagon and glucose levels in 6 normal young men. Placebo unaffected GH, insulin, glucagon, glucose and ghrelin levels. SRIF and CST similarly inhibited (p < 0.05) spontaneous GH secretion of about 90%. After SRIF or CST withdrawal, GH levels recovered to baseline levels. Both SRIF and CST similarly inhibited (p<0.01) insulin secretion of about 45%. In both sessions, after SRIF or CST withdrawal, insulin overrode baseline levels. Both SRIF and CST similarly inhibited (p < 0.01) glucagon levels of about 40%. After SRIF or CST withdrawal, glucagon persisted lower (p < 0.05) than at baseline. Neither SRIF nor CST modified glucose levels. Both SRIF and CST similarly inhibited (p < 0.01) circulating ghrelin levels of about 55%. Ghrelin levels progressively decreased from time +15 min, reaching the nadir at 120 and 105 min for SRIF and CST, respectively. Even 30 min after SRIF or CST withdrawal, ghrelin levels persisted lower (p < 0.05) than those at baseline. In conclusion, this study first shows that SRIF and CST strongly inhibits ghrelin secretion that, differently from GH and insulin secretion, persists inhibited even after stopping the infusion of SRIF or CST.
 ...
PMID:Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans. 1236 82

Ghrelin modulates somatotroph, lactotroph, corticotroph, and insulin secretion and glucose metabolism. To clarify the influence of gender and age on the endocrine actions of ghrelin in humans, we studied the effects of ghrelin (1.0 micro g/kg iv) or placebo on GH, prolactin (PRL), ACTH, cortisol, insulin, glucagon, and glucose levels in 18 young subjects (YS) and 16 elderly subjects (ES) of both genders. The GH response to GHRH (1.0 micro g/kg iv) was also studied. The GH response to ghrelin in YS was higher (P < 0.01) than in ES and both higher (P < 0.01) than to GHRH, without gender-related differences. In YS ghrelin also induced: 1) gender-independent increase (P < 0.01) in PRL, ACTH, and cortisol levels; 2) gender-independent increase in glucose levels (P < 0.01); 3) decrease (P < 0.01) in insulin levels in male YS; and 4) no change in glucagon. In ES, ghrelin induced gender-independent PRL, ACTH, and cortisol responses (P < 0.01). In ES ghrelin elicited gender-independent transient decrease in insulin (P < 0.01) coupled with increase in glucose levels (P < 0.05). In conclusion, the GH-releasing effect of ghrelin is independent of gender but undergoes age-related decrease. The effect of ghrelin on lactotroph and corticotroph secretion is age and gender independent. In both ES and YS, ghrelin influences insulin secretion and glucose metabolism.
 ...
PMID:The endocrine response to ghrelin as a function of gender in humans in young and elderly subjects. 1267 36

Ghrelin, a novel growth hormone releasing peptide, was recently isolated from stomach. We have cloned and characterized the 5(')-flanking region, containing from -2000 to -1 upstream from the translation start site of the human ghrelin gene. There was neither typical GC nor CAAT box but there were a TATATAA element and putative binding sites for several transcription factors. Ghrelin promoter was activated only in human stomach derived ECC10 cells among several cell lines examined. Functional analysis showed that promoter activity was increased by deletion of nucleotides from -2000 to -605 whereas it was decreased by further deletion and that the TATATAA element is not functioning. Glucagon and its second messenger cAMP enhanced the promoter activity, suggesting that stimulated transcription of ghrelin gene by glucagon might be responsible for increased ghrelin production during fasting at least in part. These initial characterizations will facilitate further studies of the regulatory mechanisms for ghrelin gene expression.
 ...
PMID:Cloning and characterization of the 5(')-flanking region of the human ghrelin gene. 1273 15

Ghrelin is produced mainly by endocrine cells in the stomach and is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). It also influences feeding behavior, metabolic regulation, and energy balance. It affects islet hormone secretion, and expression of ghrelin and GHS-R in the pancreas has been reported. In human islets, ghrelin expression is highest pre- and neonatally. We examined ghrelin and GHS-R in rat islets during development with immunocytochemistry and in situ hybridization. We also studied the effect of ghrelin on insulin secretion from INS-1 (832/13) cells and the expression of GHS-R in these cells. We found ghrelin expression in rat islet endocrine cells from mid-gestation to 1 month postnatally. Islet expression of GHS-R mRNA was detected from late fetal stages to adult. The onset of islet ghrelin expression preceded that of gastric ghrelin. Islet ghrelin cells constitute a separate and novel islet cell population throughout development. However, during a short perinatal period a minor subpopulation of the ghrelin cells co-expressed glucagon or pancreatic polypeptide. Markers for cell lineage, proliferation, and duct cells revealed that the ghrelin cells proliferate, originate from duct cells, and share lineage with glucagon cells. Ghrelin dose-dependently inhibited glucose-stimulated insulin secretion from INS-1 (832/13) cells, and GHS-R was detected in the cells. We conclude that ghrelin is expressed in a novel developmentally regulated endocrine islet cell type in the rat pancreas and that ghrelin inhibits glucose-stimulated insulin secretion via a direct effect on the beta-cell.
 ...
PMID:Ghrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells. 1496 97

We combined in vitro and in vivo methods to investigate the effects of ghrelin, a novel gastric hormone, on insulin and glucagon release. Studies of isolated mouse islets showed that ghrelin concentrations in the physiological range (0.5-3 nmol l(-1)) had no effect on glucose-stimulated insulin release, while low ghrelin concentrations (1-100 pmol l(-1)) inhibited and high (0.1 and 1 micromol l(-1)) stimulated. The insulin response to glucose was enhanced in the presence of a high ghrelin concentration (100 nmol l(-1)). Glucagon release was stimulated by ghrelin (0.1 pmol l(-1) to 1 micromol l(-1)); this effect was maintained in the presence of glucose (0-20 mmol l(-1)). In intact mice, basal plasma insulin was suppressed by 1 and 10 nmol kg(-1) of ghrelin, 2 and 6 min after i.v. injection. Ghrelin (0.2-10 nmol kg(-1) i.v.) suppressed also the glucose-stimulated insulin response and impaired the glucose tolerance (at a ghrelin dose of 3.3 nmol kg(-1)). Ghrelin (1 or 10 nmol kg(-1) i.v.) inhibited the insulin response to the phospholipase C stimulating agent carbachol and enhanced the insulin response to the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX) but did not affect the response to the membrane-depolarizing amino acid l-arginine. These observations suggest that the inhibitory effect of ghrelin on glucose-induced insulin release is in part exerted on phospholipase C pathways (and not on Ca(2+)entry), while the stimulatory effect of high doses of ghrelin depends on cyclic AMP. In contrast to the spectacular glucagon-releasing effect of ghrelin in vitro, ghrelin did not raise plasma glucagon. Carbachol, IBMX and l-arginine stimulated glucagon release. These responses were impaired by ghrelin, suggesting that it suppresses the various intracellular pathways (phospholipase C, cyclic AMP and Ca(2+)), that are activated by the glucagon secretagogues. Together these observations highlight (but do not explain) the different effects of ghrelin on glucagon release in vitro and in vivo. The results show that ghrelin has powerful effects on islet cells, suggesting that endogenous ghrelin may contribute to the physiological control of insulin and glucagon release. However, the narrow "window" of circulating ghrelin concentrations makes this doubtful.
 ...
PMID:Effects of ghrelin on insulin and glucagon secretion: a study of isolated pancreatic islets and intact mice. 1500 30

The gastrointestinal tract and the pancreas release hormones regulating satiety and body weight. Ghrelin stimulates appetite, and glucagon-like peptide-1, oxyntomodulin, peptide YY, cholecystokinin, and pancreatic polypeptide inhibit appetite. These gut hormones act to markedly alter food intake in humans and rodents. Obesity is the current major cause of premature death in the United Kingdom, killing almost 1000 people per week. Worldwide, its prevalence is accelerating. There is currently no effective answer to the pandemic of obesity, but replacement of the low levels of peptide YY observed in the obese may represent an effective antiobesity therapy.
 ...
PMID:Minireview: Gut peptides regulating satiety. 1504 53

The discovery of the adiposity signal leptin a decade ago revolutionised our understanding of the hypothalamic mechanisms underpinning the central control of ingestive behaviour. Subsequently, the structure and function of various hypothalamic peptide systems (Neuropeptide Y (NPY), Orexins, Melanocortins, Cocaine and Amphetamine Regulating Transcript (CART), Galanin/Galanin Like Peptides (GALP) and endocannabinoids) have been characterised in detail in rodent models. The therapeutic benefit of targeting these systems remains to be discovered. More is becoming known about the pharmacological potential of peripheral, meal-induced, episodic endogenous peptides. Hormones such as Cholecystokinin (CCK), Gastrin Releasing Peptides (GRP), Glucagon-Like Peptide I (GLP-1) Enterostatin, Amylin, Peptide YY (PYY) and Ghrelin are released prior to, during and/or after a meal, controlling intake and subjective feelings of appetite (hunger and satiety). In addition, there is an expanding body of literature detailing the effects of a wide variety of drugs on human appetite and food intake. Some of these drugs act upon CNS monoamine systems such as Serotonin (5-HT). Dopamine (DA) and Noradrenaline (NA), have long been implicated in appetite regulation. Detailed examination of both the effect of agonising endogenous gut peptide systems and the effect of various monoaminergic drugs on the expression of human appetite can provide a greater understanding of mechanisms underpinning normal appetite regulation. However, such an understanding must be based on knowledge of the effect of the treatment on meal size, eating rate, meal pattern, food choice and the subjective experience of appetite flux (hunger and satiety), and notjust food intake.
 ...
PMID:The pharmacology of human appetite expression. 1505 9


1 2 3 4 5 6 7 8 9 10 Next >>