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)

The pre-proglucagon derived peptides, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are both involved in a wide variety of peripheral functions, such as glucose homeostasis, gastric emptying, intestinal growth, insulin secretion as well as the regulation of food intake. Pre-proglucagon is also found in the brainstem in a small population of nerve cells in the nucleus of the solitary tract (NTS) that process the pre-propeptide as in the gut to yield GLP-1 and GLP-2. GLP-1 containing nerve fibres and the GLP-1 receptor are found predominantly in hypothalamic midline nuclei. GLP-1 given centrally to naive rats results in a marked induction of c-Fos protein in the supraoptic nucleus, paraventricular nucleus of the hypothalamus (PVN) and central nucleus of the amygdala, but only a moderate increase in the arcuate nucleus. The pattern of c-Fos activation is compatible with the appetite suppressing effects of GLP-1. This anorectic effect of GLP-1 appears to be mediated by the PVN, as direct injections of GLP-1 into this nucleus cause anorexia without concomitant taste aversion, suggesting a specific action upon neuronal circuits involved in the regulation of feeding. Recent experiments have also shown that GLP-1 is implicated in mediating signals from the gastrointestinal tract pertaining to discomfort and malaise. The distribution of the co-localised peptide, GLP-2, displays a perfect overlap with GLP-1 in the CNS with the highest concentration in the diffuse ventral part of the dorsomedial nucleus (DMHv). In contrast to the widely distributed GLP-1 receptor mRNA, GLP-2 receptor mRNA is exclusively expressed in the compact part of the DMH (DMHc). Interestingly, the DMHc is also the only nucleus responding to central administration of GLP-2 with a significant increase in the number of c-Fos positive cells. When injected into the lateral ventricle, GLP-2 has a marked inhibitory effect on feeding. The effect of GLP-2 on feeding is both behaviourally and pharmacologically specific. Future experiments will elucidate whether or not GLP-1 and GLP-2 are involved in the long-term or short-term regulation of feeding behaviour and hence have an impact on bodyweight.
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PMID:Glucagon-like peptide containing pathways in the regulation of feeding behaviour. 1184 Feb 14

The present study examined possible interactions between central glucagon-like peptide-1 (GLP-1) and oxytocin (OT) neural systems by determining whether blockade of GLP-1 receptors attenuates OT-induced anorexia and vice versa. Male rats were acclimated to daily 4-h food access. In the first experiment, rats were infused centrally with GLP-1 receptor antagonist or vehicle, followed by an anorexigenic dose of synthetic OT. Access to food began 20 min later. Cumulative food intake was measured every 30 min for 4 h. In the second experiment, rats were infused with OT receptor blocker or vehicle, followed by synthetic GLP-1 [(7-36) amide]. Subsequent food intake was monitored as before. The anorexigenic effect of OT was eliminated in rats pretreated with the GLP-1 receptor antagonist. Conversely, GLP-1-induced anorexia was not affected by blockade of OT receptors. In a separate immunocytochemical study, OT-positive terminals were found closely apposed to GLP-1-positive perikarya, and central infusion of OT activated c-Fos expression in GLP-1 neurons. These findings implicate endogenous GLP-1 receptor signaling as an important downstream mediator of anorexia in rats after activation of central OT neural pathways.
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PMID:GLP-1 receptor signaling contributes to anorexigenic effect of centrally administered oxytocin in rats. 1206 35

Five callitrichids (three common marmosets -Callithrix jacchus -, a black tufted-eared marmoset -C. penicillata-, and a saddle-back tamarin -Saguinus fuscicollis) were diagnosed with islet hyperplasia by histopathology and immunohistochemistry. All were privately-owned, unrelated callitrichids ranging from 2- to 4-year-old. Relevant findings were anorexia (3/5), vomiting (2/5), ptyalism (1/5), polyuria/polydipsia (1/5), respiratory distress (1/5), hyperglycemia (2/3) and glycosuria (1/1); hyperglycemia and glycosuria were associated with pregnancy in a common marmoset and resolved after reducing simple carbohydrates in diet. All five animals died, three of them after few premonitory signs; in two cases, other concurrent diseases unrelated to islet hyperplasia were considered the cause of death. Additional animals from two facilities had high weight (4), physical obesity (3), polyuria/polydipsia/polyphagia/uriposia (1), hyperglycemia (1), and/or glycosuria (2). Pathologic findings in the deceased callitrichids were: islet hyperplasia (5/5); hemosiderosis (5/5); lipomatosis (4/5) of several tissues (atria, 3/5; pancreas, gall bladder, intestine, esophagus, and thyroid, 2/5; liver, 1/5); pancreatic necrosis or steatonecrosis, and/or acute pancreatitis (3/5); and vacuolation of hepatocytes and renal tubular cells most likely consistent with hepatorenal lipidosis (2/5). The islets of Langerhans were more numerous and larger than in a control, and morphologically normal in all cases, except in a common marmoset that had a few cells with a foamy cytoplasm and shrunken hyperchromatic or picknotic nucleus. Insulin (5/5), glucagon (3/5), and somatostatin (3/5) immunohistochemistry revealed that most cells stained positively for insulin diffusely in their cytoplasm (5/5) (staining restricted to the vascular pole of b-cells in the control). These findings suggest that obesity, insulin resistance and/or type II diabetes may be implicated and thus a prospective study on these diseases in callitrichids is necessary to determine their etiopathogenesis.
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PMID:Islet hyperplasia in callitrichids. 1214 99

Intracerebroventricular administration of glucagon-like peptide-1 (7-36) amide (GLP-1) reduces food intake and produces symptoms of visceral illness, such as a conditioned taste aversion (CTA). The central hypothesis of the present work is that separate populations of GLP-1 receptors mediate the anorexia and taste aversion associated with GLP-1 administration. To test this hypothesis, we first compared the ability of various doses of GLP-1 to induce anorexia or CTA when administered into either the lateral or fourth ventricle. Lateral and fourth ventricular GLP-1 resulted in reduction of food intake at similar doses, whereas only lateral ventricular GLP-1 resulted in a CTA. Such data indicate that both hypothalamic and caudal brainstem GLP-1 receptors are likely to participate in the ability of GLP-1 to reduce food intake. We also hypothesized that the site that must mediate the ability of GLP-1 to induce visceral illness is in the central nucleus of the amygdala (CeA). Administration of 0.2 or 1.0 microg of GLP-1 (7-36) but not the inactive GLP-1 (9-36) resulted in a strong CTA with no accompanying anorexia. In addition, bilateral CeA administration of 2.5 microg of a GLP-1 receptor antagonist before intraperitoneal administration of the toxin lithium chloride resulted in a diminished CTA. Together, these data indicate that separate GLP-1 receptor populations mediate the multiple responses to GLP-1. These results indicate that GLP-1 is a flexible system that can be activated under various circumstances to alter the ingestion of nutrients and/or produce other visceral illness responses, depending on the ascending pathways of the GLP-1 system that are recruited.
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PMID:The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness. 1245 Nov 46

Glucagon-like peptide 2 (GLP-2) may mediate in part the rapid growth effects of luminal nutrients in the small intestine of newborns. The objectives of this study were to determine plasma GLP-2 concentrations and small intestinal GLP-2 receptor (GLP-2R) mRNA abundance (measured by reverse transcription polymerase chain reaction) during pre- and postnatal development and the relationship between these variables and small intestinal growth in enterally and parenterally fed fetal and newborn pigs (premature and term-delivered, 92 and 100% gestation, respectively). Plasma GLP-2 concentrations increased before birth, peaked in suckling 1-d-old pigs (87 +/- 14 pmol/L, P < 0.05), decreased with weaning-related anorexia (34 +/- 5 pmol/L, P < 0.05) and increased when normal food intake resumed (81 +/- 9 pmol/L, P < 0.05). Plasma GLP-2 concentrations were increased 1 d after enteral infusion of colostrum in fetal pigs at 92% gestation compared with untreated controls (59 +/- 11 vs. 7 +/- 2 pmol/L, P < 0.05). In newborn pigs, plasma GLP-2 was increased 2-6 d after the enteral administration of a milk diet, compared with the parenteral infusion of elemental nutrients, but the time course of the response was delayed in premature newborn pigs. Small intestinal GLP-2R mRNA abundance was highest at birth and decreased with enteral food intake in fetal, suckling and weaned pigs (P < 0.05). In contrast, enteral feeding increased (P < 0.05) relative small intestinal weight and/or villous heights in these pigs. We conclude that the introduction of enteral feeding transiently increases plasma GLP-2 concentrations and decreases small intestinal GLP-2R mRNA levels during pig development. GLP-2 may play a role in the growth of the small intestine around birth and weaning via a response to enteral nutrition.
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PMID:Introduction of enteral food increases plasma GLP-2 and decreases GLP-2 receptor mRNA abundance during pig development. 1277 17

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

We report a case of glucagonoma syndrome, revealed by a necrolytic migratory erythema that had developed for four Years, associated with anorexia, severe weight loss, anemia, hypoprotidemia, and hypoaminoacidemia. The fasting blood glucose level tended paradoxically to be low (0.6 g/l). Elevated plasma glucagon levels confirmed our diagnosis. The absence of diabetes was explained by an independent insulin secretion derived from this composite pancreatic tumor, authenticated by the histological analysis and the proinsulin level. This level was similar to those typically observed in insulinomas. Six Months after a complete surgical exeresis, symptoms disappeared and biological results returned to normal values.
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PMID:[Necrolytic migratory erythema revealing glucagonoma without diabetes]. 1503 34

The central glucagon-like peptide-1 (GLP-1) system has been implicated in the control of feeding behavior. Here we explore GLP-1 mediation of the anorexic response to administration of systemic LPS and address the relative importance of caudal brain stem and forebrain GLP-1 receptor (GLP-1-R) for the mediation of the response. Fourth-intracerebroventricular delivery of the GLP-1-R antagonist exendin-(9-39) (10 microg) did not itself affect food intake in the 24 h after injection but significantly attenuated the otherwise robust (approximately 60%) reduction in food intake obtained after LPS (100 microg/kg) treatment. This result highlights a role for caudal brain stem GLP-1-R in the mediation of LPS anorexia but does not rule out the possibility that forebrain receptors also contribute to the response. Forebrain contribution was addressed by delivery of the GLP-1-R antagonist to the third ventricle with the caudal flow of cerebrospinal fluid blocked by occlusion of the cerebral aqueduct. Exendin-(9-39) delivery thus limited to forebrain did not attenuate the anorexic response to LPS. These data suggest that LPS anorexia is mediated, in part, by release of the native peptide acting on GLP-1-R within the caudal brain stem.
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PMID:Attenuation of lipopolysaccharide anorexia by antagonism of caudal brain stem but not forebrain GLP-1-R. 1547 2

In rats, central administration of glucagon-like peptide-1 (GLP-1) elicits symptoms of visceral illness like those caused by the toxin lithium chloride (LiCl), including anorexia, conditioned taste aversion (CTA) formation, and neural activation in the hypothalamus and hindbrain including activation of brainstem preproglucagon cells. Most compellingly, pharmacological antagonists of the GLP-1 receptor (GLP-1R) block several effects of LiCl in rat. The major goal of these experiments was to further test the hypothesis that the central nervous system GLP-1 system is critical to the visceral illness actions of LiCl by using mice with a targeted disruption of the only described GLP-1R. First, we observed that, like the rat, LiCl activates preproglucagon neurons in wild-type mice. Second, GLP-1R -/- mice demonstrated normal anorexic and CTA responses to LiCl. To test the possibility that alternate GLP-1Rs mediate aversive effects, we examined the ability of GLP-1 to produce a CTA in GLP1R -/- mice. Although lateral ventricular GLP-1 produced a CTA in wild-type mice, it did not produce a CTA in GLP-1R -/- mice. Furthermore, the same GLP-1R antagonist that can block the aversive effects of LiCl in the rat failed to do so in the mouse. These results support the conclusion that in mouse, unlike in rat, GLP-1R signaling is not required for the visceral illness response to LiCl. Such species differences are an important consideration when comparing results from rat and mouse studies.
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PMID:The role of central glucagon-like peptide-1 in mediating the effects of visceral illness: differential effects in rats and mice. 1545 18

Cholecystokinin (CCK), glucose dependent insulinotropic peptide (GIP), and glucagon-like peptide 1 (GLP-1) regulate satiety as enterogastrons and incretins. They also directly affect the satiety centers. Therefore, these peptides may participate in the pathogenesis of eating disorders. CCK, GIP, and GLP-1 secretion were studied in 13 adolescent girls suffering from simple obesity, 13 girls with anorexia nervosa, and 10 healthy girls. Each girl was subjected to an oral glucose tolerance test (OGTT) and standard meal test. Blood was collected before stimulation and at 15, 30, 60, and 120 min. The concentrations of all peptides were determined by RIA commercial kits. Fasting and postprandial levels of these peptides as well as integrated outputs were measured. High postprandial levels of CCK observed in the girls with anorexia may aggravate the course of this disease by intensifying nausea and vomiting. Low postprandial level of GLP-1 in girls with simple obesity may be responsible for excessive ingestion of food and weaker inhibition of gastric emptying, which also leads to obesity.
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PMID:Cholecystokinin, glucose dependent insulinotropic peptide and glucagon-like peptide 1 secretion in children with anorexia nervosa and simple obesity. 1564 96


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