Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we established a radioimmunoassay (RIA) specific for ghrelin from the bullfrog Rana catesbeiana using a novel antibody raised against the C-terminal amino acid sequence of bullfrog ghrelin [13-28]. We also examined the distribution of ghrelin-producing cells in the stomachs of bullfrogs using this antibody and a cRNA probe specific for the bullfrog ghrelin gene. Ghrelin levels in plasma and stomach extracts were approximately 150 fmol/ml and 83-135 fmol/mg wet tissue, respectively. Reverse-phase high performance liquid chromatographic analysis, combined with bullfrog ghrelin RIA, revealed that ghrelin immunoreactivity in the stomach was composed of non-acylated ghrelin (des-acyl ghrelin) and several acylated forms of ghrelin bearing different fatty acid modifications, which could induce increases in intracellular Ca2+ in cells expressing the rat GH secretagogue receptor. In the stomach, the major storage form was acylated ghrelin. In bullfrog plasma, however, the majority of ghrelin immunoreactivity was des-acyl ghrelin and C-terminal fragments of frog ghrelin. Acylated ghrelin forms comprised only minor peaks. Ghrelin-immunopositive and ghrelin mRNA-expressing cells were observed within the mucosal layer of the stomach. Following starvation, significant increases in plasma ghrelin levels and stomach ghrelin mRNA levels were observed as early as 10 days after starvation. These results indicate that ghrelin is present in the stomach and plasma of the bullfrog, which can be detected with our novel antibody. Interestingly, the primary storage form of ghrelin in the stomach differed from the circulating form dominating in the plasma. Furthermore, increases in ghrelin levels in plasma and mRNA levels in the stomach after starvation suggest the possible involvement of ghrelin in energy homeostasis in the bullfrog.
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PMID:Identification of immunoreactive plasma and stomach ghrelin, and expression of stomach ghrelin mRNA in the bullfrog, Rana catesbeiana. 1663 Jun 19

Ghrelin is upregulated under negative energy balance conditions, including starvation and hypoglycemia, while it is downregulated under situations of positive energy balance, such as feeding, hyperglycemia and obesity. The aims of this study were to assess potential ghrelin interactions with glucose levels in appetite control and to identify potential mechanisms involving orexigenic and anorexigenic ghrelin mediated signals by using a specific anti-ghrelin antibody. Our results confirm that peripheral ghrelin is an important signal in meal initiation and food intake stimulation. C-fos positive neurons in the PVN increased after insulin or 2-deoxyglucose administration. Moreover, we also demonstrate that peripheral ghrelin blockade with a specific anti-ghrelin antibody reduces, in part, the orexigenic signal induced by insulin and 2-DG administration. Furthermore, when we blocked peripheral ghrelin, c-fos positive CRF neurons and CART expression increased in the PVN, both under hypoglycemia or cytoglycopenia conditions, suggesting a neuronal activation (anorexigenic signalling) in this hypothalamic region. In summary, our findings imply that peripheral ghrelin plays an important role in regulatory "glucostatic" feeding mechanisms due to its role as a "hunger" signal affecting the PVN area, which may contribute to energy homeostasis through both orexigenic/anorexigenic pathways.
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PMID:Peripheral ghrelin participates in glucostatic feeding mechanisms and in the anorexigenic signalling mediated by CART and CRF neurons. 1666 99

The brainstem is essential for mediating energetic response to starvation. Brain stem TRH is synthesized in caudal raphe nuclei innervating brainstem and spinal vagal and sympathetic motor neurons. Intracisternal injection (ic) of a stable TRH analog RX77368 (7.5-25 ng) dose-dependently stimulated solid food intake by 2.4- to 3-fold in freely fed rats, an effect that lasted for 3 h. By contrast, RX77368 at 25 ng injected into the lateral ventricle induced a delayed and insignificant orexigenic effect only in the first hour. In pentobarbital-anesthetized rats, RX77368 (50 ng) ic induced a significant bipeak increase in serum total ghrelin levels from the basal of 8.7+/-1.7 ng/ml to 13.4+/-2.4 ng/ml at 30 min and 14.5+/-2.0 ng/ml at 90 min, which was prevented by either bilateral vagotomy (-60 min) or atropine pretreatment (2 mg/kg, -30 min) but magnified by bilateral adrenalectomy (-60 min). TRH analog ic-induced food intake in freely fed rats was abolished by either peripheral atropine or ghrelin receptor antagonist (D-Lys-3)-GHRP-6 (10 micromol/kg) or ic Y1 receptor antagonist 122PU91 (10 nmol/5 microl). Brain stem TRH mRNA and TRH receptor 1 mRNA increased by 57-58 and 33-35% in 24- and 48-h fasted rats and returned to the fed levels after a 3-h refeeding. Natural food intake in overnight fasted rats was significantly reduced by ic TRH antibody, ic Y1 antagonist, and peripheral atropine. These data establish a physiological role of brainstem TRH in vagal-ghrelin-mediated stimulation of food intake, which involves interaction with brainstem Y1 receptors.
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PMID:Brainstem thyrotropin-releasing hormone regulates food intake through vagal-dependent cholinergic stimulation of ghrelin secretion. 1695 36

Obestatin is a recently discovered 23 amino acids peptide derived from the ghrelin gene. As opposed to ghrelin, obestatin was shown to inhibit food intake in mice. The aims of this research were to study the effects of acute obestatin treatment on feeding behavior in the rat and its effects on GH and corticosterone secretion. Our results demonstrate that in young-adult male rats, obestatin effectively blunts the hunger caused by short-term starvation. Obestatin did not modify GH secretion in 10-day-old rats and did not antagonize the GH-releasing effects of hexarelin. Moreover, obestatin administration had no effects on spontaneous corticosterone secretion. In conclusion, these data demonstrate that in young-adult male rats the newly discovered obestatin can inhibit feeding but does not modify GH and corticosterone release in infant rats.
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PMID:Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat. 1703 54

Man ingests food to mitigate hunger (mediated by physiological and biochemical signals), satisfy appetite (subjective sensation) and because of psychosocial reasons. Satiation biomarkers (stop feeding) are gastric distention and hormones (CCK, GLP-1) and satiety biomarkers (induce feeding) are food-induced thermogenesis, body temperature, glycaemia and also hormones (insulin, leptin and ghrelin). Oxidative metabolism/body composition, tryptophan/serotonin and proinflammatory cytokines are also implicated on hunger physiology. At the present time, ghrelin is the only known circulating orexigenic with potential on hunger/body weight regulation. It is a neuropeptide (endogenous ligand for the GH secretagogue) recently isolated from the oxyntic mucosa and synthesized mainly in the stomach. Its blood concentration depends on diet, hyperglucemia and adiposity/leptin. It is secreted 1-2 hours preprandially and its concentration decreases drastically during the postprandium. Ghrelin acts on the lateral hypothalamus and theoretically inhibits proinflammatory cytokine secretion and antagonizes leptin. Ghrelin physiologically increases food intake and stimulates adipogenesis, gastrointestinal motility and gastric acid secretion, and has other hormonal and cardiovascular functions. Ghrelin blood concentration is reduced in massive obesity, non-alcoholic steatohepatitis, polycystic ovary syndrome, acromegaly, hypogonadism, ageing, short bowel syndrome and rheumatoid arthritis; and increased in primary or secondary anorexia, starvation, chronic liver disease and celiac disease. Cerebral and peritoneal ghrelin administration (rats) and systemic administration (rats and healthy volunteers, cancer patients or patients on peritoneal dialysis) promotes food consumption and increases adiposity, of utmost importance in the treatment of patients with anorexia.
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PMID:[Ghrelin: beyond hunger regulation]. 1705 87

Among its pleiotropic actions, ghrelin modulates insulin secretion and glucose metabolism. Herein we investigated the role of ghrelin in pancreatic beta-cell proliferation and apoptosis induced by serum starvation or interferon (IFN)-gamma/TNF-alpha, whose synergism is a major cause for beta-cell destruction in type I diabetes. HIT-T15 beta-cells expressed ghrelin but not ghrelin receptor (GRLN-R), which binds acylated ghrelin (AG) only. However, both unacylated ghrelin (UAG) and AG recognized common high-affinity binding sites on these cells. Either AG or UAG stimulated cell proliferation through Galpha(s) protein and prevented serum starvation- and IFN-gamma/TNF-alpha-induced apoptosis. Antighrelin antibody enhanced apoptosis in either the presence or absence of serum but not cytokines. AG and UAG even up-regulated intracellular cAMP. Blockade of adenylyl cyclase/cAMP/protein kinase A signaling prevented the ghrelin cytoprotective effect. AG and UAG also activated phosphatidyl inositol 3-kinase (PI3K)/Akt and ERK1/2, whereas PI3K and MAPK inhibitors counteracted the ghrelin antiapoptotic effect. Furthermore, AG and UAG stimulated insulin secretion from HIT-T15 cells. In INS-1E beta-cells, which express GRLN-R, AG and UAG caused proliferation and protection against apoptosis through identical signaling pathways. Noteworthy, both peptides inhibited cytokine-induced NO increase in either HIT-T15 or INS-1E cells. Finally, they induced cell survival and protection against apoptosis in human islets of Langerhans. These expressed GRLN-R but showed also UAG and AG binding sites. Our data demonstrate that AG and UAG promote survival of both beta-cells and human islets. These effects are independent of GRLN-R, are likely mediated by AG/UAG binding sites, and involve cAMP/PKA, ERK1/2, and PI3K/Akt.
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PMID:Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3',5'-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling. 1706 44

Ghrelin is mainly produced by the stomach, although it is expressed in other tissues, including the pancreas. Among its pleiotropic actions, ghrelin prevents the development of diabetes in rats and exerts mitogenic and antiapoptotic effects in different cell types. In addition, a ghrelin-producing epsilon-cell population has been demonstrated in rodent islets, suggesting a direct role in the control of islet cell survival. In this study, we investigated the effect of acylated ghrelin (AG) and unacylated ghrelin (UAG) on cell survival of HIT-T15 pancreatic beta cells. We show that both AG and UAG equally prevented beta cell death induced by serum withdrawal. In addition, both peptides inhibited serum starvation-induced apoptosis. These findings indicate that UAG and AG prevent cell death and apoptosis of pancreatic beta cells. Since only AG, but not UAG, binds the GRLN receptor, a different and as yet unknown receptor is likely involved in these survival mechanisms.
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PMID:Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HIT-T15 pancreatic beta-cells. 1711 4

Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells. Ghrelin physiologically induces food intake and seems to alter lipid and glucid metabolism in several tissues such as adipose tissue and liver. Liver has a key position in lipid metabolism as it allows the metabolic orientation of fatty acids between oxidation and esterification. We investigated the effects of peripheral ghrelin administration on 2 crucial parameters of fatty acid oxidation: the levocarnitine (L-carnitine)-dependent entry of the fatty acids in the mitochondria and the mitochondrial fatty acid oxidation. Ghrelin was either given to rats prior to the hepatocyte preparation and culture or used to treat hepatocytes prepared from control animals. Direct incubation of ghrelin to raw hepatocytes did not induce any change in the studied parameters. In hepatocytes prepared from 3 nmol ghrelin-treated rats, a 44% reduction of the mitochondrial fatty acid oxidation while no alteration of the L-carnitine-related parameters were observed. These results suggested (a) that ghrelin has no direct effect on liver, and (b) that when administrated to a whole organism, ghrelin may alter the lipid metabolism and the energy balance through a marked decrease in liver fatty acid oxidation.
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PMID:Ghrelin reduces hepatic mitochondrial fatty acid beta oxidation. 1755 59

It has been shown that the ghrelin receptor, GH secretagogue receptor (GHS-R), is synthesized in neurons of the nodose ganglion and then transmitted to axon terminals, where it binds to ghrelin. The orexigenic signal of ghrelin secreted from the stomach is transmitted to the brain via the vagal afferent nerve. To explore the regulation of GHS-R synthesis in the nodose ganglion, we examined whether or not GHS-R type a mRNA expression shows circadian rhythm, and is affected by starvation, vagotomy, or i.v. administration of gastrointestinal peptides. Nodose ganglion GHS-R mRNA levels showed a diurnal rhythm, being high during periods of light and low during darkness. Although starvation tended to increase the level of GHS-R mRNA, a more significant increase was observed upon re-feeding. Vagotomy decreased the level of GHS-R mRNA significantly in comparison with animals that underwent a sham procedure. Cholecystokinin and gastrin increased the level of GHS-R mRNA after 2 h, but after 4 h, the level decreased. These results suggest that GHS-R synthesis in the nodose ganglion is regulated centrally and peripherally by neuronal and humoral information, and that these dynamic changes of GHS-R mRNA expression may be involved in the regulation of feeding by ghrelin.
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PMID:Regulation of GH secretagogue receptor gene expression in the rat nodose ganglion. 1759 19

Ghrelin is a novel appetite-inducing peptide hormone secreted by the stomach. The purpose of this study was first to identify the cDNA encoding sequence for ghrelin in sea bass (Dicentrarchus labrax). Using molecular cloning techniques we sequenced the cDNA corresponding to sea bass ghrelin mRNA. A total of 798 bases including a 5'-untranslated region (89 bp), an open reading frame (ORF) (324 bp), and a 3'-untranslated region (385 bp) were detected. Nucleotide sequence (ORF) encoded a 108 amino acid prepropeptide that demonstrated complete conservation of the N-terminal "biological active core" (GSSF) of the predicted mature ghrelin peptide. We also analyzed fasting-induced changes in the expression of ghrelin mRNA, using a one-tube two-temperature real-time RT-PCR with which the gene expression can be absolutely quantified using the standard curve method. Our results revealed that ghrelin was highly expressed in the stomach with much lower levels of expression in the proximal intestine and brain. Levels of ghrelin mRNA in the stomach were upregulated under conditions of negative energy balance, such as starvation, and downregulated during positive energy balance, such as refeeding. These findings offer new information about the sea bass ghrelin gene and support a role of this orexigenic hormone in the regulation of food intake in sea bass.
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PMID:Sea bass ghrelin: molecular cloning and mRNA quantification during fasting and refeeding. 1759 23


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