Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ghrelin gene peptides include acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob). AG, mainly produced by the stomach, exerts its central and peripheral effects through the GH secretagogue receptor type 1a (GHS-R1a). UAG, although devoid of GHS-R1a-binding affinity, is an active peptide, sharing with AG many effects through an unknown receptor. Ob was discovered as the G-protein-coupled receptor 39 (GPR39) ligand; however, its physiological actions remain unclear. The endocrine pancreas is necessary for glucose homeostasis maintenance. AG, UAG, and Ob are expressed in both human and rodent pancreatic islets from fetal to adult life, and the pancreas is the major source of ghrelin in the perinatal period. GHS-R1a and GPR39 expression has been shown in beta-cells and islets, as well as specific binding sites for AG, UAG, and Ob. Ghrelin colocalizes with glucagon in alpha-islet cells, but is also uniquely expressed in epsilon-islet cells, suggesting a role in islet function and development. Indeed, AG, UAG, and Ob regulate insulin secretion in beta-cells and isolated islets, promote beta-cell proliferation and survival, inhibit beta-cell and human islet cell apoptosis, and modulate the expression of genes that are essential in pancreatic islet cell biology. They even induce beta-cell regeneration and prevent diabetes in streptozotocin-treated neonatal rats. The receptor(s) mediating their effects are not fully characterized, and a signaling crosstalk has been suggested. The present review summarizes the newest findings on AG, UAG, and Ob expression in pancreatic islets and the role of these peptides on beta-cell development, survival, and function.
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PMID:Unraveling the role of the ghrelin gene peptides in the endocrine pancreas. 2059 21

Acyl ghrelin, a 28-amino acid peptide hormone, is the endogenous cognate ligand for the growth hormone secretagogue receptor. Ghrelin is involved in stimulating growth hormone release, eliciting feeding behavior, inducing adiposity and stimulating gastrointestinal motility. Ghrelin is unique for its post-translational modification of O-n-octanoylation at serine 3 through ghrelin O-acyltransferase, and is the only peripheral signal to enhance food intake. Plasma ghrelin levels manifest "biphasic changes" in diabetes mellitus (DM). In the early stage of DM, the stomach significantly increases the secretion of ghrelin into the plasma, and elevated plasma ghrelin levels are correlated with diabetic hyperphagic feeding and accelerated gastrointestinal motility. In the late stage of DM, plasma ghrelin levels may be lower, which might be linked with anorexia/muscle wasting, delayed gastrointestinal transit, and even gastroparesis. Therefore, the unique ghrelin system may be the most important player compared to the other hindgut hormones participating in the "entero-insular axis". Further studies using either knockdown or knockout of ghrelin gene products and ghrelin O-acyltransferase may unravel the pathogenesis of DM, and show benefits in combating this disease and metabolic syndrome.
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PMID:Modulation of ingestive behavior and gastrointestinal motility by ghrelin in diabetic animals and humans. 2068 86

Ghrelin and peptide YY (PYY) are brain-gut peptides that have a variety of physiological functions and are involved in energy regulation. Thus far, abnormalities in the expression and secretion of ghrelin and PYY are known to occur in lifestyle-related diseases, including obesity, and the improvement of these abnormalities has become an important challenge. Exercise has recently been reported to influence ghrelin and PYY concentrations. Exercise increases the PYY secretion. The effects of exercise on ghrelin levels vary with the study subject, timing of exercise, and duration of exercise. Here, we review the findings of recent studies on the association of PYY and ghrelin with obesity, particularly, on the influence of exercise on PYY and ghrelin levels.
Exp Clin Endocrinol Diabetes 2011 Mar
PMID:Effects of exercise on the levels of peptide YY and ghrelin. 2069 71

Ghrelin and its receptor are important regulators of metabolic functions, including appetite, energy expenditure, fat accumulation, and growth hormone (GH) secretion. The ghrelin receptor is characterized by an ability to signal even without any ligand present with approximately 50% of the maximally ghrelin-induced efficacy-a feature that may have important physiological implications. The high basal signaling can be modulated either by administration of specific ligands or by engineering of mutations in the receptor structure. [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P was the first inverse agonist to be identified for the ghrelin receptor, and this peptide has been used as a starting point for identification of the structural requirements for inverse agonist properties in the ligand. The receptor binding core motif was identified as D-Trp-Phe-D-Trp-Leu-Leu, and elongation of this peptide in the amino-terminal end determined the efficacy. Attachment of a positively charged amino acid was responsible for full inverse agonism, whereas an alanin converted the peptide into a partial agonist. Importantly, by use of mutational mapping of the residues critical for the modified D-Trp-Phe-D-Trp-Leu-Leu peptides, it was found that space-generating mutations in the deeper part of the receptor improved inverse agonism, whereas similar mutations located in the more extracellular part improved agonism. Modulation of the basal signaling by mutations in the receptor structure is primarily obtained by substitutions in an aromatic cluster that keep TMs VI and VII in close proximity to TM III and thus stabilize the active conformation. Also, substitution of a Phe in TM V is crucial for the high basal activity of the receptor as this residue serves as a partner for Trp VI:13 in the active conformation. It is suggested that inverse agonist and antagonist against the ghrelin receptor provide an interesting possibility in the development of drugs for treatment of obesity and diabetes and that improved structural understanding of the receptor function facilitates the drug development.
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PMID:Modulation of the constitutive activity of the ghrelin receptor by use of pharmacological tools and mutagenesis. 2103 26

Ghrelin has wide effects on cardiovascular and endocrine system. The aims of this study are to investigate the direct damage effect of high glucose and high palmitate on cardiomyocyte, and to study the effect of ghrelin on insulin resistance induced by glucotoxicity/lipotoxicity in cardiomyocyte and the possible mechanism underlying the cardioprotective activities of ghrelin. The changes of [(3)H]-2-deoxy-d-glucose ((3)H-G) intake rates were detected by isotope tracer method and the gene expressions in insulin signal transduction pathway were detected by real-time PCR and Western blot assay. The (3)H-G intake rate significantly reduced in high glucose (25mmol/l) or high palmitate (0.5mmol/l) treated primary rat ventricular myocytes. After the treatment of ghrelin (10(-7)mol/l), the (3)H-G intake rate recovered to the normal level. In addition, the phosphorylation of AKT occurred in 10min and was the highest in 30min after the stimulation with ghrelin, which can be blocked by phosphoinositide 3-kinase (PI3K) inhibitor, LY2940002. Ghrelin also increased the mRNA levels of glucose transporter 4 (GLUT4), peroxisome proliferators (PPARr) and AMP activated protein kinase (AMPK) genes in insulin signal transduction pathway. These results indicate that the direct damage of high glucose and high palmitate on cardiomyocyte might be through insulin resistance (IR). Ghrelin can inhibit gluco/lipotoxicity induced insulin resistance by PI3K/AKT pathway. This may provide a clue for therapy for myocardial disease in diabetes mellitus.
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PMID:Ghrelin inhibits insulin resistance induced by glucotoxicity and lipotoxicity in cardiomyocyte. 2109 96

Ghrelin is a novel GH-releasing peptide, which has been identified as an endogenous ligand for GH-secretagogue receptor. Ghrelin is mainly secreted by the stomach and plays a critical role in a variety of physiological processes including endocrine, metabolic, cardiovascular, immunological, and other actions. Ghrelin stimulates food intake via hypothalamic neurons and causes a positive energy balance and body weight gain by decreasing fat utilization and promoting adiposity. Given the multiple effects of ghrelin, its potential clinical applications have been evaluated in various conditions. Preliminary trials have shown that it may prove valuable in the management of disease-induced cachexia. Ghrelin may improve the wasting syndrome through GH-dependent or GH-independent effects. Moreover, ghrelin may play a role in the management of disorders of gut motility and obesity. Finally, other potential clinical applications of ghrelin include the treatment of patients with diabetes mellitus, infections, rheumatological diseases or GH deficiency and the diagnosis of this hormonal disorder.
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PMID:Current and potential roles of ghrelin in clinical practice. 2129 71

The increasing prevalence of metabolic syndrome and the consequent cardiovascular diseases, like atherosclerotic diseases and Type 2 diabetes has stimulated an active search for novel risk factors. The hormones regulating energy balance are of special interest as potential risk factors for metabolic syndrome and Type 2 diabetes. Ghrelin is a peptide hormone from stomach with growth hormone releasing activity. It is also able to modify glucose and insulin metabolism, blood pressure levels, adipogenesis, and inflammatory processes in experimental conditions. Whether ghrelin has a role in the development metabolic syndrome and the associated diseases, is not known. This review will report the evidence for the role of ghrelin in the clustering of the components of the metabolic syndrome.
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PMID:Ghrelin in Type 2 diabetes mellitus and metabolic syndrome. 2141 92

Ghrelin is a peptide hormone that has been isolated from the stomach and localized to endocrine cells in the oxyntic mucosa. Ghrelin acts synergistically with GH-releasing hormone and increases appetite and feeding. It also accelerates gastric and small intestinal motility in rodents. Patients with diabetes suffer from slow gastric emptying, giving rise to nausea and vomiting. The present study was undertaken to establish the possible role of ghrelin in slow gastric emptying observed in patients with longstanding type 1 diabetes, and to correlate the results with the metabolic status of these patients. Eleven patients with type 1 diabetes along with 10 and 15 healthy volunteers as controls underwent gastrointestinal endoscopy/biopsy or gastric scintigraphy. Gastric emptying in patients and controls was measured by scintigraphy. Sections from biopsies of the oxyntic mucosa and duodenum were immunostained for ghrelin with the avidin-biotin complex method. The density of the cells was quantified with computerized image analysis. Both the lag phase and half-emptying time (T50) were higher in patients with diabetes than in healthy volunteers. The T50 was correlated with the blood glucose level. The density of ghrelin-immunoreactive cells in the oxyntic mucosa of patients with diabetes was significantly reduced compared to the healthy controls. Ghrelin cell density was correlated with both the lag phase and T50, as well as with blood glucose level. The present finding of reduced density of ghrelin cells in patients with type 1 diabetes, which was well correlated with gastric emptying, indicates the possible role of ghrelin in the pathophysiology of gastroparesis observed in diabetes.
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PMID:Low density of ghrelin cells in the oxyntic mucosa correlated to slow gastric emptying in patients with type 1 diabetes. 2147 17

Ghrelin is a growth hormone secretagogue produced by the gut, and is expressed in the hypothalamus and other tissues as well. Ghrelin not only plays an important role in the regulation of appetite, energy balance and glucose homeostasis, but also shows anti-bacterial activity, suppresses pro-inflammatory cytokine production and restores gut barrier function. In experimental animals, ghrelin has shown significant beneficial actions in preventing mortality from sepsis. In the critically ill, corticosteroid insufficiency as a result of dysfunction of the hypothalamic-pituitary-adrenal axis is known to occur. It is therefore possible that both gut and hypothalamus play an important role in the pathogenesis of sepsis by virtue of their ability to produce ghrelin, which, in turn, could be a protective phenomenon to suppress inflammation. It remains to be seen whether ghrelin and its analogues are of benefit in treating patients with sepsis.
World J Diabetes 2011 Jan 15
PMID:Relationship between gut and sepsis: Role of ghrelin. 2153 44

Recent evidence highlights an important role of ghrelin in glucose homeostasis. In this review we provide a detailed summary of recent advances in this field. We describe the effects of ghrelin on all aspects of glucose homeostasis including glucose-stimulated insulin secretion, hepatic glucose production and insulin stimulated glucose disposal in the peripheral tissues. The existing evidence suggests ghrelin primarily inhibits insulin release from the pancreas and we highlight an important mechanism involving AMPK-UCP2 ATP-stimulated potassium channels and intracellular calcium regulation. Ghrelin increases hepatic glucose production and prevents glucose disposal in muscle and adipose tissues, which collectively leads to hyperglycemia and impaired glucose tolerance. We discuss the important role ghrelin plays in glucose homeostasis during different metabolic states. During severe calorie restriction, ghrelin increases blood glucose concentrations in order to maintain glucose homeostasis. In diet-induced obesity, ghrelin exacerbates hyperglycemia and promotes a diabetic phenotype.
Curr Diabetes Rev 2011 May
PMID:A recent update on the role of ghrelin in glucose homeostasis. 2153 9


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