Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020175 (hunger)
 5,670 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 is a recently identified orexigenic hormone secreted by the stomach and has been implicated in meal-time hunger. Several experiments demonstrate a transient surge in ghrelin secretion shortly before a scheduled meal, suggesting from the involvement of cephalic mechanisms. If ghrelin secretion is stimulated by hunger in sheep, plasma levels of ghrelin should be modified by different feeding regimens that affect hunger drive. To test this hypothesis, we investigated changes in plasma ghrelin concentrations in fed Suffolk rams ad libitum and in rams either twice or four times daily. Plasma ghrelin levels increased (P<0.05) abruptly just before every feeding period in sheep fed twice and four times daily and then fell shortly after feeding. Peak levels of the pre-prandial ghrelin surge were higher (P<0.01) in animals fed twice daily than in animals fed four times daily, leading to greater (P<0.05) areas under response curves over 12h. In contrast, the plasma ghrelin levels remained relatively low and constant in sheep fed ad libitum, with no evidence of surges in plasma ghrelin levels. These results confirm that the transient surge in plasma ghrelin levels occurs just before feeding and demonstrate that this can be modified by the feeding regimen in sheep.
 ...
PMID:A transient surge of ghrelin secretion before feeding is modified by different feeding regimens in sheep. 1241 23

Prader-Willi syndrome (PWS) is a genetic disorder occurring in 1 of 10,000-16,000 live births and is characterized by excessive appetite with progressive massive obesity as well as short stature and mental retardation. Most patients have GH deficiency and hypogonadotropic hypogonadism. The causes of the hyperphagia and abnormal GH secretion are unknown. To determine whether ghrelin, a novel GH secretagogue with orexigenic properties, is elevated in PWS, we measured fasting plasma ghrelin concentration; body composition (dual-energy x-ray absorptiometry); and subjective ratings of hunger (visual analog scale) in seven subjects (6 males and 1 female; age, 26 +/- 7 yr; body fat, 39 +/- 11%, mean +/- SD) with PWS (diagnosis confirmed by genetic test) and 30 healthy subjects (reference population, 15 males and 15 females; age, 32 +/- 7 yr; body fat, 36 +/- 11%) fasted overnight. All subjects were weight stable for at least 6 months before admission to the study. The mean plasma ghrelin concentration was higher in PWS than in the reference population (307 +/- 164 vs. 109 +/- 24 fmol/ml; P < 0.001), and this difference remained significant after adjustment for percentage body fat (P < 0.001). Plasma ghrelin was also higher (P = 0.0004) in PWS than in five healthy subjects fasted for 36 h. A positive correlation was found between plasma ghrelin and subjective ratings of hunger (r = 0.71; P = 0.008). Furthermore, in subjects with PWS, the concentration of the hormone was not different before and after ingestion of 2 ml and a satiating amount of the same liquid meal (ghrelin concentrations: 307 +/- 164 vs. 306 +/- 205 vs. 260 +/- 134 fmol/ml, respectively; ANOVA for repeated measures, P = 0.56). This is the first evidence that ghrelin, a novel orexigenic hormone, is elevated in subjects with PWS. Our finding suggests that ghrelin may be responsible, at least in part, for the hyperphagia observed in PWS.
 ...
PMID:High circulating ghrelin: a potential cause for hyperphagia and obesity in prader-willi syndrome. 1246 37

In order to develop an effective pharmacological treatment for obesity, an endogenous factor that promotes a positive energy balance by increasing appetite and decreasing fat oxidation could represent the drug target scientists have been looking for. The recently discovered gastric endocrine agent ghrelin, which appears to be the only potent hunger-inducing factor to naturally circulate in our blood stream, was discovered in 1999. Since then the acylated peptide hormone ghrelin has evolved from an endogenous growth hormone secretagogue to a regulator of energy balance to a pleiotropic hormone with multiple sources, numerous target tissues and most likely several physiological functions. Although neither the exact mechanism of action by which ghrelin increases food intake and adiposity is known, nor the putatively differential effects of brain-derived and stomach-derived ghrelin on energy homeostasis have been determined, blocking or neutralizing ghrelin action still seems one of the more reasonable pharmacological approaches to reverse a chronically positive energy balance. However, based on growing experience with compounds targeting the neuroendocrine regulation of energy balance, it is quite possible that a ghrelin antagonist will either fail to cure obesity due to the existence of compensatory mechanisms or undesired effects might reveal the true biological function of ghrelin (e.g. cardiovascular mechanisms, anti-proliferative effects, reproduction).
 ...
PMID:Ghrelin as a potential anti-obesity target. 1276 30

The gastric peptide ghrelin augments and the adipocyte-derived hormone leptin reduces appetite and food intake. In the central nervous system, insulin directly decreases hunger sensation but could also act indirectly by modulating ghrelin and leptin secretion. This study examines dose-dependent effects of insulin on plasma ghrelin and leptin concentrations during hyperinsulinemic (1, 2, and 4 mU x kg(-1) x min(-1))-euglycemic clamp tests in six nondiabetic (control subjects) and six type 2 diabetic patients. Type 2 diabetic patients were studied before and after prolonged (12-h and 67-h) variable intravenous insulin treatment aiming at near-normoglycemia (115 +/- 4 mg/dl). Nondiabetic subjects were also studied during saline infusion, which did not affect ghrelin but decreased leptin by 19 +/- 6% (P < 0.03). In control subjects, plasma ghrelin decreased at all clamp steps (-17 +/- 1, -27 +/- 6, and -33 +/- 4%, respectively; P < 0.006 vs. baseline), whereas leptin increased by 35 +/- 11% (P < 0.05). In type 2 diabetic patients without insulin treatment, ghrelin decreased by 18 +/- 7% (P < 0.05) only after 4 mU x kg(-1) x min(-1) insulin infusion and leptin increased by 19 +/- 6% (P < 0.05). After prolonged insulin treatment and near-normoglycemia, ghrelin and leptin remained unchanged in type 2 diabetic patients during the clamps. In conclusion, insulin reduces plasma ghrelin in nondiabetic patients and, to a lesser extent, in type 2 diabetic patients before insulin therapy. These findings indicate an indirect effect of insulin via ghrelin on the suppression of hunger sensation and appetite.
 ...
PMID:Insulin-dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabetic patients. 1282 48

Aging is associated with a reduction in appetite and food intake, predisposing to protein-energy malnutrition. The causes of this "anorexia of aging" are largely unknown. To investigate possible contributions of enhanced satiating effects of cholecystokinin (CCK) and reduced stimulation of food intake by ghrelin, eight undernourished older women [age, 80.4 +/- 2.6 yr; body mass index (BMI), 16.9 +/- 0.57 kg/m(2)], eight well-nourished older women (age, 77 +/- 0.9 yr; BMI, 23.7 +/- 0.8 kg/m(2)), and eight well-nourished young women (age, 22 +/- 1.3 yr; BMI, 20.5 +/- 0.4 kg/m(2)), in randomized order, ate on 1 d a 280-kCal preload and on the other no preload, 90 min before an ad libitum meal. At baseline the undernourished, but not the well-nourished, older subjects were less hungry (P < 0.05) than young subjects. Before and after the preload, plasma CCK levels were higher (P < 0.05) in the older than young subjects, with no difference between the older groups. Plasma ghrelin concentrations were higher in the undernourished than both well-nourished groups and decreased similarly after the preload in all groups. The preload suppressed food intake in the well-nourished older and young subjects (P < 0.05), but was without effect in the undernourished old. These observations suggest that reduced basal hunger, rather than increased meal-induced satiety, contributes to the anorexia of aging and that changes in CCK and ghrelin are unlikely to be responsible.
 ...
PMID:Appetite, food intake, and plasma concentrations of cholecystokinin, ghrelin, and other gastrointestinal hormones in undernourished older women and well-nourished young and older women. 1291 64

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.
 ...
PMID:Oxyntomodulin suppresses appetite and reduces food intake in humans. 1455 43

The stimulation of exocrine pancreatic secretion that has been attributed by Pavlov exclusively to various reflexes (nervism), was then found that it depend also on numerous enterohormones, especially cholecystokinin (CCK) and secretin, released by duodeno-jejunal mucosa and originally believed to act via an endocrine pathway. Recently, CCK and other enterohormones were found to stimulate the pancreas by excitation of sensory nerves and triggering vago-vagal and entero-pancreatic reflexes. Numerous neurotransmitters and neuropeptides released by enteric nervous system (ENS) of gut and pancreas have been also implicated in the regulation of exocrine pancreas. This article was designed to review the contribution of vagal nerves and entero-hormones, especially CCK and other enterohormones, involved in the control of appetitive behavior such as leptin and ghrelin and pancreatic polypeptide family (peptide YY and neuropeptide Y). Basal secretion shows periodic fluctuations with peals controlled by ENS and by motilin and Ach. Plasma ghrelin, that is considered as hunger hormone, increases under basal conditions, while plasma leptin falls to the lowest level. Postprandial pancreatic secretion, classically divided into cephalic, gastric and intestinal phases, involves predominantly CCK, which under physiological conditions acts almost entirely by activation of vago-vagal reflexes to stimulate the exocrine pancreas, being accompanied by the fall in plasma ghrelin and increase of plasma leptin, reflecting feeding behavior. We conclude that the major role in postprandial pancreatic secretion is played by vagus and gastrin in cephalic and gastric phases and by vagus in conjunction with CCK and secretin in intestinal phase. PP, PYY somatostatin, leptin and ghrelin that affect food intake appear to participate in the feedback control of postprandial pancreatic secretion via hypothalamic centers.
 ...
PMID:Brain-gut axis in pancreatic secretion and appetite control. 1456 70

The effects of specific nutritional factors on ghrelin secretion have not been investigated in humans. Therefore, we assessed ghrelin responses to a high-carbohydrate meal (1217 kcal with 77% carbohydrates, 10% protein, and 13% lipids) and to an isocaloric high-fat meal (15% carbohydrates, 10% proteins, and 75% lipids) in 14 nonobese healthy women. Eleven subjects also rated their hunger feelings on visual analog scales. Circulating ghrelin abruptly fell after both meals, but, after the carbohydrate meal, its maximum percent decrease was significantly greater than after the fat meal (P = 0.02). Plasma insulin and glucose levels rose after the meals, but their increases were significantly higher after the carbohydrate meal than after the fat meal. No significant change was observed in circulating leptin after both meals. Moreover, compared with the fat meal, the carbohydrate meal had a significantly greater suppressant effect on hunger feelings. Plasma ghrelin changes were significantly associated with hunger changes (P < 0.007). These findings show that circulating ghrelin is differently suppressed by diet manipulations. The mechanisms responsible for such a phenomenon and its possible implication in the physiology of human satiety remain to be elucidated.
 ...
PMID:Differential responses of circulating ghrelin to high-fat or high-carbohydrate meal in healthy women. 1460 98

The importance of the central melanocortin system in the regulation of energy balance is highlighted by studies in transgenic animals and humans with defects in this system. Mice that are engineered to be deficient for the melanocortin-4 receptor (MC4R) or pro-opiomelanocortin (POMC) and those that overexpress agouti or agouti-related protein (AgRP) all have a characteristic obese phenotype typified by hyperphagia, increased linear growth, and metabolic defects. Similar attributes are seen in humans with haploinsufficiency of the MC4R. The central melanocortin system modulates energy homeostasis through the actions of the agonist, alpha-melanocyte-stimulating hormone (alpha-MSH), a POMC cleavage product, and the endogenous antagonist AgRP on the MC3R and MC4R. POMC is expressed at only two locations in the brain: the arcuate nucleus of the hypothalamus (ARC) and the nucleus of the tractus solitarius (NTS) of the brainstem. This chapter will discuss these two populations of POMC neurons and their contribution to energy homeostasis. We will examine the involvement of the central melanocortin system in the incorporation of information from the adipostatic hormone leptin and acute hunger and satiety factors such as peptide YY (PYY(3-36)) and ghrelin via a neuronal network involving POMC/cocaine and amphetamine-related transcript (CART) and neuropeptide Y (NPY)/AgRP neurons. We will discuss evidence for the existence of a similar network of neurons in the NTS and propose a model by which this information from the ARC and NTS centers may be integrated directly or via adipostatic centers such as the paraventricular nucleus of the hypothalamus (PVH).
 ...
PMID:The central melanocortin system and the integration of short- and long-term regulators of energy homeostasis. 1474 11


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