Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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PMID:Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. 1175 31

The importance of the melanocortin system in obesity has been confirmed by the recent discovery of mutations in the melanocortin MC4 receptor in morbidly obese patients and the finding that intranasal administration of a fragment of melanocortin decreases body fat in humans. Transgenic mice overexpressing melanin-concentrating hormone (MCH) are obese and a second MCH receptor has been identified. In addition, ghrelin, endocannabinoids and glucagon-like peptide 2 have been identified as potentially important central regulators of food intake.
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PMID:Hypothalamic peptides as drug targets for obesity. 1175 22

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.
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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.
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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.
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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.
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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.
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PMID:Cloning and characterization of the 5(')-flanking region of the human ghrelin gene. 1273 15

After nursing, pups of the northern elephant seal (Mirounga angustirostris) are approximately 46% body fat and rely almost entirely on the oxidation of their large fat stores to sustain their metabolism for the ensuing 8-12 week postweaning fast, which is a natural component of their life history. Thus, fasting pups provide an ideal opportunity to examine the hormonal alterations associated with prolonged food deprivation in a naturally adapted model. Cortisol, ghrelin, glucagon, growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin, blood urea nitrogen (BUN), glucose and non-esterified fatty acids (NEFA) were examined in 20 male and 20 female pups blood sampled early (<1 week postweaning) and late (6-8 weeks postweaning) during the fast. Mean cortisol, ghrelin, GH, and glucagon increased 1.8-, 1.8-, 1.4-, and 2.3-fold between early and late periods, while mean IGF-I and insulin decreased 97% and 38%, respectively. NEFA increased 2.3-fold, while BUN and glucose decreased 46% and 11%, respectively. NEFA was significantly and positively correlated with cortisol and GH; individually; however, when the relationship was examined as a multiple regression the correlation improved suggesting that cortisol and GH act synergistically to promote lipolysis during the fast. GH and BUN were negatively and significantly correlated between early and late fasting suggesting that GH may promote protein sparing as well. The decrease in glucose may be responsible for stimulating glucagon, resulting in the maintenance of relative hyperglycemia. The increases in cortisol, ghrelin, glucagon, and GH suggest that these hormones may be integral in mediating the metabolism of seal pups during prolonged fasting.
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PMID:GH and ghrelin increase with fasting in a naturally adapted species, the northern elephant seal (Mirounga angustirostris). 1296 44

Oxyntomodulin (OXM) is released from the gut postprandially, in proportion to energy intake, and circulating levels of OXM are elevated in several conditions associated with anorexia. Central injection of OXM reduces food intake and weight gain in rodents, suggesting that OXM signals food ingestion to hypothalamic appetite-regulating circuits. We investigated the effect of iv OXM (3.0 pmol/kg.min) on appetite and food intake in 13 healthy subjects (body mass index, 22.5 +/- 0.9 kg/m(2)) in a randomized, double-blind, placebo-controlled, cross-over study. Infusion of OXM significantly reduced ad libitum energy intake at a buffet meal (mean decrease, 19.3 +/- 5.6%; P < 0.01) and caused a significant reduction in scores for hunger. In addition, cumulative 12-h energy intake was significantly reduced by infusion of OXM (mean decrease, 11.3 +/- 6.2%; P < 0.05). OXM did not cause nausea or affect food palatability. Preprandial levels of the appetite-stimulatory hormone, ghrelin, were significantly suppressed by OXM (mean reduction, 44 +/- 10% of postprandial decrease; P < 0.0001). Elevated levels of endogenous OXM associated with disorders of the gastrointestinal tract may contribute to anorexia.
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PMID:Oxyntomodulin suppresses appetite and reduces food intake in humans. 1455 43

The central regulation of the food intake is organized by a long-loop mechanism involving humoral signals and afferent neuronal pathways to the hypothalamus, obligatory processing in hypothalamic neuronal circuits, and descending commands through vagal and spinal neurons to the body. Receptors sensitive to glucose metabolism, body fat reserves, distension of the stomach, as well as neuropeptide and cannabinoid receptors have been identified and localized in the hypothalamus. Five groups of cells in the hypothalamus--arcuate, paraventricular, ventromedial and dorsomedial nuclei, and the dorsolateral hypothalamic area--contain neurons with either anorexic actions (alpha-MSH, CART peptide, corticotropin-releasing hormone, urocortin III, cholecystokinin, glucagon-like peptides) or that stimulate food intake (neuropeptide Y, agouti-related peptide, orexins, melanin concentrating hormone, galanin). Intrahypothalamic neuronal circuits exist between these peptidergic neurons including the arcuate-paraventricular and arcuate-dorsolateral hypothalamic projections. Circulating substances carrying signals connected to changes in body food homeostasis and energy balance (leptin, ghrelin, insulin, glucose) enter the hypothalamus mainly through the arcuate nucleus. Neurons in the medulla oblongata that express leptin and insulin receptors, as well as neuropeptide mediators project to the hypothalamus. Vica versa, hypothalamic neurons give rise to projections to autonomic centers in the brainstem and the spinal cord with potential for stimulation or inhibition of food intake, energy balance and ingestion behavior.
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PMID:Hypothalamic regulation of food intake. 1460 50


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