Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heterotrimeric G proteins of the Gq/11 family transduce signals from a variety of neurotransmitter and hormone receptors and have therefore been implicated in various functions of the nervous system. Using the Cre/loxP system, we generated mice which lack the genes coding for the alpha subunits of the two main members of the Gq/11 family, gnaq and gna11, selectively in neuronal and glial precursor cells. Mice with defective gnaq and gna11 genes were morphologically normal, but they died shortly after birth. Mice carrying a single gna11 allele survived the early postnatal period but died within 3 to 6 weeks as anorectic dwarfs. In these mice, postnatal proliferation of pituitary somatotroph cells was strongly impaired, and plasma growth hormone (GH) levels were reduced to 15%. Hypothalamic levels of GH-releasing hormone (GHRH), an important stimulator of somatotroph proliferation, were strongly decreased, and exogenous administration of GHRH restored normal proliferation. The hypothalamic effects of ghrelin, a regulator of GHRH production and food intake, were reduced in these mice, suggesting that an impairment of ghrelin receptor signaling might contribute to GHRH deficiency and abnormal eating behavior. Taken together, our findings show that Gq/11 signaling is required for normal hypothalamic function and that impairment of this signaling pathway causes somatotroph hypoplasia, dwarfism, and anorexia.
Mol Cell Biol 2005 Mar
PMID:Loss of Gq/11 family G proteins in the nervous system causes pituitary somatotroph hypoplasia and dwarfism in mice. 1571 47

The influence of fasting and winter-acclimatization (cold and short-day acclimatization) on mouse plasma leptin, ghrelin, growth hormone (GH) and melatonin concentrations was determined from blood samples taken at mid-day and midnight. A 16-h fast decreased the plasma leptin but almost doubled the plasma ghrelin concentrations which contribute to energy saving, appetite stimulation and, in the case of leptin, to inhibition of reproduction. Winter-acclimatization did not affect plasma ghrelin concentrations, whereas leptin decreased to the same level as in fasting. The low leptin concentrations possibly enable an increased caloric intake for the purpose of thermogenesis. Fasting and winter-acclimatization seemed to abolish the diurnal leptin rhythm, but had no effect on that of ghrelin. Plasma melatonin concentration correlated negatively with ghrelin, suggesting a possible role for melatonin in the regulation of ghrelin concentration. SNS-activity and insulin appear to be the main regulators of leptin plasma concentration in the mouse, rather than melatonin as in some seasonal mammals. Interestingly, endogenous ghrelin did not stimulate GH secretion, which is a well-documented reaction to exogenous ghrelin injections.
Comp Biochem Physiol A Mol Integr Physiol 2005 Feb
PMID:Role of adiposity hormones in the mouse during fasting and winter-acclimatization. 1574 62

Ghrelin and peptide YY (PYY) are peptides generally produced by the gastrointestinal organs which are involved in appetite regulation via highly specialized centers in the brain. Abnormal plasma ghrelin and PYY levels compared with controls have been reported for subjects with Prader-Willi syndrome (PWS) which is characterized by infantile hypotonia, poor suck reflex and failure to thrive followed by hyperphagia and marked obesity in early childhood. We studied gene expression of ghrelin, peptide YY, and their receptors (i.e., GHS-R1a, GHS-R1b, and NPY2R) in six different brain regions (frontal cortex, temporal cortex, visual cortex, pons, medulla, and hypothalamus) obtained from three subjects with PWS, two individuals with Angelman syndrome, and six controls to determine if expression of these genes is detectable in different regions of the brain in subjects with and without PWS. In general, expression of these genes using RT-PCR was detected in all subjects and no obvious differences were seen in their pattern of expression between subjects with or without PWS. Additional studies including quantitative gene expression measurements will be required to further evaluate the role of these genes in the eating disorder seen in PWS.
Int J Mol Med 2005 Apr
PMID:Ghrelin, peptide YY and their receptors: gene expression in brain from subjects with and without Prader-Willi syndrome. 1575 36

Although obesity is an epidemic threat to general health worldwide, an effective treatment has yet to be found. Insights into weight-regulatory pathways will accelerate the identification of new molecular targets for anti-obesity agents. 5'-AMP-activated protein kinase (AMPK) is an enzyme activated during low cellular energy charge. In peripheral tissues, the activation of AMPK influences various metabolic pathways, including glucose uptake, glycolysis, and fatty acid oxidation, all of which help to re-establish a normal cellular energy balance. AMPK is also present in the neurons of the hypothalamus, a critical center in the regulation of energy homeostasis. Recent studies from our group and others have shown that many factors (alpha-lipoic acid, leptin, insulin, ghrelin, glucose, 2-deoxyglucose, etc.) cause an alteration in hypothalamic AMPK activity that mediates effects on feeding behavior. Hypothalamic AMPK also appears to play a role in the central regulation of energy expenditure and peripheral glucose metabolism. These data indicate that hypothalamic AMPK is an important signaling molecule that integrates nutritional and hormonal signals and modulates feeding behavior and energy metabolism.
J Mol Med (Berl) 2005 Jul
PMID:Role of hypothalamic 5'-AMP-activated protein kinase in the regulation of food intake and energy homeostasis. 1580 19

Two nonpeptide (L692,429 and MK-677) and two peptide [GH-releasing peptide (GHRP)-6 and ghrelin] agonists were compared in binding and in signal transduction assays: calcium mobilization, inositol phosphate turnover, cAMP-responsive element (CRE), and serum-responsive element (SRE) controlled transcription, as well as arrestin mobilization. MK-677 acted as a simple agonist having an affinity of 6.5 nm and activated all signal transduction systems with similar high potency (0.2-1.4 nm). L-692,429 also displayed a very similar potency in all signaling assays (25-60 nm) but competed with a 1000-fold lower apparent affinity for ghrelin binding and surprisingly acted as a positive allosteric receptor modulator by increasing ghrelin's potency 4- to 10-fold. In contrast, the potency of GHRP-6 varied 600-fold (0.1-61 nm) depending on the signal transduction assay, and it acted as a negative allosteric modulator of ghrelin signaling. Unexpectedly, the maximal signaling efficacy for ghrelin was increased above what was observed with the hormone itself during coadministration with the nonendogenous agonists. It is concluded that agonists for the ghrelin receptor vary both in respect of their intrinsic agonist properties and in their ability to modulate ghrelin signaling. A receptor model is presented wherein ghrelin normally only activates one receptor subunit in a dimer and where the smaller nonendogenous agonists bind in the other subunit to act both as coagonists and as either neutral (MK-677), positive (L-692,429), or negative (GHRP-6) modulators of ghrelin function. It is suggested that an optimal drug candidate could be an agonist that also is a positive modulator of ghrelin signaling.
Mol Endocrinol 2005 Sep
PMID:Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling. 1590 59

Ghrelin was originally purified and characterized in rats and humans as the first identified endogenous ligand of the growth hormone secretagogue receptor. In mammals, ghrelin is mainly produced in the stomach, with minor levels of ghrelin present in the brain and various other tissues. Ghrelin is involved in the regulation of many physiological functions including the regulation of growth hormone secretion and food intake in mammals. The gene and peptide structures of ghrelin have been recently identified in several fish species. As in mammals, ghrelin mRNA is mainly expressed in the gut of fish. Ghrelin is involved in the regulation of a number of physiological functions, including the regulation of pituitary hormone release and the stimulation of food intake in fish. In this review, we wish to provide an up-to-date discussion on the structure, distribution and functions of ghrelin in fish, in comparison to ghrelin in other vertebrates.
Comp Biochem Physiol A Mol Integr Physiol 2005 Apr
PMID:Structure, distribution and physiological functions of ghrelin in fish. 1593 98

Although des-acyl ghrelin is thought of as a non-functional peptide, studies show that it decreases food intake and gastric emptying in mice. However, no studies have examined the effects of centrally administered des-acyl ghrelin on food intake and gastrointestinal transit in rats. We investigated the effects of intracisternal (IC) administration of des-acyl ghrelin on food intake in free-feeding and food-deprived rats, as well as on the gastrointestinal transit in conscious rats. IC injection of des-acyl ghrelin dose-dependently (0.1 and 1.0 nmol/rat) decreased 20-min, 1-h and 2-h cumulative food intake in 16-h food-deprived, but not free-feeding rats, while IC administration of O-n-octanoylated (acylated) ghrelin (1 nmol/rat) increased food intake in both fed and fasted rats. IC-administered des-acyl ghrelin dose-dependently inhibited charcoal semi-liquid gastric emptying (0.01, 0.1, 0.3 and 1.0 nmol/rat) compared to saline-injected controls, but did not affect the geometric center and running percentage of small intestinal transit. However, IC acylated ghrelin enhanced gastric emptying and geometric center of small intestinal transit, but did not change running percentage of small intestinal transit. The studies suggest that IC des-acyl ghrelin decreases food intake in food-deprived rats and inhibits gastric emptying without altering small intestinal transit. These results establish the role of des-acyl ghrelin in regulating food intake as well as gastric emptying.
Int J Mol Med 2005 Oct
PMID:Intracisternal des-acyl ghrelin inhibits food intake and non-nutrient gastric emptying in conscious rats. 1614 7

Ghrelin affects not only growth hormone secretion but also nutrient utilization and metabolic hormone secretion in humans and experimental animals. The effects of ghrelin on plasma metabolic hormone and metabolite levels in domestic herbivores remain unclear despite the fact that the physiological characteristics of nutrient digestion and absorption imply specific responses to ghrelin. Therefore, the effects of ghrelin on plasma glucose, pancreatic hormones and cortisol concentrations were investigated in Holstein dairy cattle in various physiological states. Ghrelin (0.3 nmol/kg) or placebo (2% bovine serum albumin in saline) was intravenously injected in pre-ruminant calves (pre-rumen function), adult non-lactating (functional rumen) and lactating cows (functional rumen and lactation), and plasma glucose, insulin, glucagon and cortisol concentrations were then determined. Ghrelin injection increased plasma glucose concentrations in adult cows, especially in lactating cows. No hyperglycemic response was observed in pre-ruminant calves. A transient rise of insulin and glucagon levels was distinctively found in lactating cows in response to the ghrelin administration. Ghrelin injection decreased the insulin level in pre-ruminant calves. Ghrelin increased cortisol secretion independently of the physiological state. The results of the present study suggest that the effects of ghrelin on plasma glucose and pancreatic hormone levels may reflect differences in the physiological states of dairy cattle.
Comp Biochem Physiol A Mol Integr Physiol 2006 Jan
PMID:Effects of ghrelin injection on plasma concentrations of glucose, pancreatic hormones and cortisol in Holstein dairy cattle. 1632 22

Numerous lines of evidence indicate that ghrelin, an endogenous ligand of the growth hormone-secretagogue receptor, is expressed in the human and rat adrenal cortex. In this study, we examined whether ghrelin gene expression undergoes changes in the human adrenal cortex during aging. Semi-quantitative real-time reverse transcription-polymerase chain reaction demonstrated a highly significant negative correlation between ghrelin mRNA and age in adrenal cortex of 27 patients (aged from 33 to 82 years), who underwent unilateral adrenalectomy/nephrectomy for kidney cancer. No significant differences in the level of adrenal ghrelin expression were observed between males and females. Since it has been previously shown that ghrelin exerts a marked growth-stimulating action on cultured adrenocortical cells, we hypothesize that the down-regulation of ghrelin gene transcription in adrenals could be associated with the reported decrease in adrenal DNA synthesis and mitogenic activity during aging.
Int J Mol Med 2006 Feb
PMID:Age-dependent decrease in the ghrelin gene expression in the human adrenal cortex: a real-time PCR study. 1639 32

Zinc is an essential nutrient with a wide range of functions and closely involved in a variety of enzymatic processes of importance in glucose, protein and lipid metabolism. Ghrelin is the endogenous ligand of the G protein coupled growth hormone secretagogue receptor. The regulatory mechanism that explain the biosynthesis and secretion of ghrelin in the gastrointestinal tract has not been clarified. This study was undertaken to examine the effect of zinc supplementation on the streptozotocin (STZ)-induced diabetic rats, which exhibits ghrelin production and secretion, and lipid metabolism on the gastrointestinal tract. The animals were divided into four groups. Group I: Non-diabetic untreated animals. Group II: Zinc-treated non-diabetic rats. Group III: STZ-induced diabetic untreated animals. Group IV: Zinc-treated diabetic animals. Zinc sulfate was given to some of the experimental animals by gavage at a dose of 100 mg/kg body weight every day for 60 days. In the zinc-treated diabetic group, the blood glucose levels decreased and body weight increased as compared to the diabetic untreated group. Zinc supplementation to STZ-diabetic rats revealed the protective effect of zinc on lipids parameters such as total lipid, cholesterol, HDL-cholesterol and atherogenic index. There is no statistically change in ghrelin-immunoreactive cells in gastrointestinal tissue. But, it has found that zinc supplementation caused a significant reduction in densities of ghrelin-producing cells of fundic mucosa of zinc-treated diabetic animals as compared to untreated, non-diabetic controls. Zinc supplementation may contribute to prevent some complications of diabetic rats, biochemically.
Mol Cell Biochem 2006 Jun
PMID:The effect of zinc supplementation on ghrelin-immunoreactive cells and lipid parameters in gastrointestinal tissue of streptozotocin-induced female diabetic rats. 1647 19


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