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)

Peptidyl-glycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is an enzyme that catalyzes conversion of glycine-extended peptides to alpha-amidated bioactive peptides. Two peptides that are processed at their carboxyl-termini by this enzyme are neuropeptide Y and anglerfish peptide Y, both of which possess a C-terminal glycine that is used as a substrate for amidation. Results from previous reports have demonstrated that neuropeptide Y-like and anglerfish peptide Y-like immunoreactivities are present in the brain of anglerfish (Lophius americanus). Furthermore, neuropeptide Y-like peptides, namely anglerfish peptide Y and anglerfish peptide YG (the homologues of pancreatic polypeptide) are present in the islet organ of this species. Neuropeptide Y has also been localized in the anterior, intermediate and posterior lobes of the pituitary gland in a variety of species. In order to learn more about the distribution of the enzyme responsible for alpha amidation of these peptides in the brain and pituitary and to specifically investigate the relationship of this enzyme to peptide synthesizing endocrine cells of the anglerfish islet, we performed an immunohistochemical study using several antisera generated against different peptide sequences of the enzyme. PAM antisera labeled cells in the islet organ, pituitary and brain, and fibers in the brain and pituitary gland. The PAM staining pattern in the brain was remarkably similar to the distribution of neuropeptide Y immunoreactivity reported previously. Clusters of cells adjacent to vessels in the anterior pituitary displayed punctate PAM immunoreactivity while varicose fibers were observed in the pituitary stalk and neurohypophysis. Endocrine cells of the islet organ were differentially labeled with different PAM antisera. Comparison of the staining patterns of insulin, glucagon, and anglerfish peptide Y in the islet organ to PAM immunoreactivity suggests a distribution of forms of PAM enzyme in insulin and anglerfish peptide Y-containing cells, but no overlap with glucagon-producing cells. The results also indicate that PAM immunoreactivity is widely distributed in the brain, pituitary and islet organ of anglerfish in cells, that contain peptides that require presence of a C-terminal glycine for amidation.
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PMID:Distribution of peptidyl-glycine alpha-amidating monooxygenase immunoreactivity in the brain, pituitary and islet organ of the anglerfish (Lophius americanus). 775 Jan 30

Neuropeptide Y (NPY) is stored in sympathetic nerves and NPY levels increase several times during exercise. NPY administration during prolonged exercise causes reduced splanchnic glucose production. To elucidate the effects of NPY on adrenaline (Adr)-stimulated splanchnic glycogenolysis these substances were infused to seven healthy subjects in the post-absorptive state. Blood samples were drawn from an arterial and a central hepatic vein catheter for determination of splanchnic blood flow, exchanges of metabolites and arterial levels of NPY, catecholamines, insulin, glucagon and renin in the basal state and during 20 min Adr infusion (0.1-0.3 nmol kg-1 min-1). After basal values were reached a 60 min NPY infusion was initiated. At 40 min of NPY infusion the Adr infusion was repeated. Adr alone increased splanchnic blood flow (41%, P < 0.01), arterial glucose concentration (29%, P < 0.001) and splanchnic glucose production (102%, P < 0.01). During the NPY infusion both splanchnic blood flow and arterial glucose fell (P < 0.05). Although the combined NPY and Adr infusion caused the same proportional increases in splanchnic blood flow, arterial glucose and splanchnic glucose production as with Adr alone the absolute values were lower (all P < 0.05). Arterial insulin as well as Adr and noradrenaline increased with the combined NPY-and Adr infusion as with Adr alone. Arterial plasma renin activity was 12% lower with the combined NPY and Adr-infusion compared to Adr infusion alone. These results indicate further an inhibitory effect of NPY on splanchnic glycogenolysis and suggest that NPY inhibits Adr-stimulated renin release.
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PMID:Inhibitory effects of neuropeptide Y on splanchnic glycogenolysis and renin release in humans. 820 50

Food intake can be increased or decreased after either central or peripheral administration of peptides. Galanin, neuropeptide Y, opioid peptides, growth hormone releasing hormone and desacetyl-MSH increase food intake whereas insulin, glucagon, cholecystokinin, anorectin, corticotropin releasing hormone, neurotensin, bombesin, enterostatin, cyclo-his-pro and thyrotropin-releasing hormone reduce food intake. A number of these peptides also affect the activity of the sympathetic nervous system. The peptides which have been tested have a reciprocal effect on food intake and sympathetic activity. Opioids, NPY and GHRH, which increase food intake, decrease sympathetic activity. Conversely, peptides which reduce food intake, increase sympathetic activity, with glucagon, cholecystokinin, corticotropin releasing hormone, calcitonin, neurotensin and bombesin being examples, Several of these peptides also affect the intake of specific nutrients. Insulin reduces food intake in animals fed a high carbohydrate diet, but not when fed a high fat diet. Neuropeptide Y increases carbohydrate intake. Galanin and opioid peptides increase fat intake. Enterostatin and cyclo-His-Pro, on the other hand reduce fat intake. Glucagon decreases protein intake. The effect of peptides on the intake of specific nutrients suggests that peptides may work in part by modulating basic feeding mechanisms to lead to the selection of specific nutrients from the diet. This hypothesis might be called a nutrient specific model of peptide-induced food intake.
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PMID:The nutrient balance hypothesis: peptides, sympathetic activity, and food intake. 848 34

1. Neuropeptide Y is a potent appetite stimulant and has been found to modulate glucose metabolism when given chronically. The acute effects of neuropeptide on peripheral glucose handling have not been studied in detail. We have studied the acute effects of central nervous system injection of neuropeptide on glucose metabolism in vivo in the rat. 2. Rats implanted with chronic cannulae in the third cerebral ventricle were injected with either neuropeptide Y or saline and peripheral insulin sensitivity was assessed during a hyperinsulinaemic euglycaemic clamp. The effect of centrally injected neuropeptide Y on post-absorptive glucose metabolism was studied using a constant infusion of [6-3H]glucose. 3. Infusion of neuropeptide Y resulted in a 18% increase in glucose requirement during the clamp, suggesting increased peripheral tissue responsiveness to insulin. Neuropeptide Y injection in 10h fasted rats increased plasma glucose (area under curve 9.9 +/- 0.2 versus 9.1 +/- 0.1 mmol h-1l-1, P < 0.01), insulin (103 +/- 23 versus 33 +/- 8 pmol/l, P < 0.01, at 30 min) and glucagon (5.5 +/- 0.5 versus 3.1 +/- 0.3 pmol/l, P < 0.05, at 30 min). The increase in plasma glucose was due to an initial increase in the rate of appearance, which peaked between 20 and 30 min after neuropeptide Y infusion; over the entire 90 min 16% more glucose entered the systemic circulation in the neuropeptide Y-treated rats than in control rats, and the total quantity of glucose removed was also greater. 4. Neuropeptide Y in the central nervous system influences glucose metabolism by altering secretion of islet hormones, hepatic glucose production and the peripheral response to insulin.
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PMID:Acute effects of central neuropeptide Y injection on glucose metabolism in fasted rats. 854 70

Neuropeptide Y (NPY) is known to occur in adrenergic and non-adrenergic nerves in rat pancreatic islets. Analysis of islet extracts has revealed local NPY synthesis after glucocorticoid treatment. The cellular localisation of NPY expression in rat islets following dexamethasone treatment (2 mg/kg daily, for 12 days), was investigated by a combination of immunocytochemistry (ICC) and in situ hybridisation (ISH). NPY-immunoreactive nerve fibres were seen in pancreatic islets of both control and dexamethasone-treated rats. In the controls weak NPY immunoreactivity but no NPY mRNA was observed in occasional islets. After dexamethasone treatment, clusters of islet cells distributed both centrally and peripherally displayed intense NPY immunoreactivity and NPY mRNA labelling. Immunocytochemical double staining and ISH combined with ICC for NPY and islet hormones revealed that most NPY expressing cells were identical with insulin cells; a few cells were identical with somatostatin or pancreatic polypeptide (PP) cells. In contrast, glucagon cells seemed to be devoid of NPY immunoreactivity and NPY mRNA labelling. Thus, in the rat, glucocorticoids cause a marked upregulation of NPY expression in islet cells, preferentially the insulin cells. The expression of NPY might represent an islet adaptation mechanism to the reduced peripheral insulin sensitivity.
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PMID:Neuropeptide Y is expressed in subpopulations of insulin- and non-insulin-producing islet cells in the rat after dexamethasone treatment: a combined immunocytochemical and in situ hybridisation study. 874 81

The ontogeny of endocrine cells and nerve fibers containing immunoreactivities for 12 regulatory peptides and serotonin was studied in the digestive tract of a flatfish, the turbot (Scophthalmus maximus), using antisera specific for mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR) endocrine cells were detected from day 5 to day 10 in stomach and intestine I. Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine I. In contrast to the islet cells, they reacted with antisera against mammalian (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti-mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present in the gastro-entero-pancreatic system and the enteric nervous system. Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP-immunoreactivities coexisted throughout development. In entero-endocrine cells, NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They seemed to contain none of the other peptides. Their number and distribution exhibited great interindividual differences. Vasoactive intestinal polypeptide (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP-IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)-IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day 17. The first serotonin (SER)-IR cells were observed in the stomach anlage around day 10 and SER-IR nerve fibers at day 15 throughout the gastro-intestinal tract. Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells were identified in the stomach anlage and intestine I around day 8 and contained NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several developmental phases can be distinguished: (1) at the onset of exogenous feeding only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a differentiated entero-endocrine system establishes during the early phase of exogenous feeding; (3) before the final differentiation of stomach and gut GAS/CCK-IR cell appear; (4) after metamorphosis most of the different types of regulatory peptide-containing nerve fibers develop, probably setting up the fine regulation of gastro-intestinal blood flow and motility.
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PMID:An immunohistochemical analysis of the ontogeny, distribution and coexistence of 12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the digestive tract of the turbot, Scophthalmus maximus (Teleostei). 900 19

The endocrine pancreas of three red frogs was studied immunohistochemically. It consisted of islets and diffuse endocrine cells. The islets showed a mammalian-like arrangement with a central core of B cells and a peripheral mantle of A/PP cells. A few D and VIP cells were also present. Several regulatory peptides were co-localized in the same endocrine cells by consecutive sections and double-labeling studies. The A/PP cells were formed by subpopulations of cells showing various types of immunoreactivity and varying degrees of immunolabeling. Generally, glucagon/pancreatic polypeptide, glucagon/pancreatic polypeptide/peptide tyrosine tyrosine and glucagon/pancreatic polypeptide/neuropeptide tyrosine immunoreactivities were present in the islets and in the endocrine cells scattered throughout the exocrine parenchyma (the diffuse component). Some specimens, mainly belonging to Rana dalmatina, showed evident periinsular halos around the islets. The diffuse component was abundant, and mainly contained A/PP cells. It formed a net across the exocrine parenchyma; its interrelationship with the latter might occur by a paracrine mechanism.
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PMID:Islets and diffuse endocrine component in the pancreas of three red frogs species: relationships between endocrine and exocrine tissue. 922 87

Neuropeptide Y (NPY) has been shown to inhibit insulin secretion from the islets of Langerhans. We show that insulin secretion in the insulinoma cell line RIN 5AH is inhibited by NPY. 125I-Peptide YY (PYY) saturation and competition-binding studies using NPY fragments and analogues on membranes prepared from this cell line show the presence of a single class of NPY receptor with a Y1 receptor subtype-like profile. Inhibition of insulin secretion in this cell line by NPY fragments and analogues also shows a Y1 receptor-like profile. Both receptor binding and inhibition of insulin secretion showed the same orders of potency with NPY > [Pro34]-NPY > NPY 3-36 >> NPY 13-36. The Y1 receptor antagonist, BIBP 3226, blocks NPY inhibition of insulin secretion from, and inhibits 125I-PYY binding to, RIN 5AH cells. Northern blot analysis using a Y1-receptor specific probe shows that NPY Y1 receptors are expressed by RIN 5AH cells. Y5 receptors are not expressed in this cell line. Neuropeptide Y inhibition of insulin secretion is blocked by incubation with pertussis toxin, implying that the effect is via a G-protein (Gi or Go) coupled receptor. Neuropeptide Y inhibits the activation of adenylyl cyclase by isoprenaline in RIN 5AH cell lysates, and the stimulation of cAMP by glucagon-like peptide-1 (7-36) amide (GLP-1). It also blocks insulin secretion stimulated by GLP-1, but not by dibutyryl cyclic AMP. Hence, we suggest that NPY inhibits insulin secretion from RIN 5AH cells via a Y1 receptor linked through Gi to the inhibition of adenylyl cyclase.
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PMID:Inhibition of glucose stimulated insulin secretion by neuropeptide Y is mediated via the Y1 receptor and inhibition of adenylyl cyclase in RIN 5AH rat insulinoma cells. 986 16

The endocrine pancreatic cells of Pseudemys scripta elegans were investigated immunocytochemically by light and electron microscopy. Insulin-, somatostatin (SST)-1, SST-28 (1-12)-, salmon (s)SST-25-, glucagon-, pancreatic polypeptide (PP)-, peptide tyrosine tyrosine (PYY)-, and neuropeptide tyrosine (NPY)-like immunoreactivities were observed. Insulin cells were immunogold labeled with bonito insulin antiserum and secretory granules were characterized by a wide halo and a dense core of varying shape. Consecutive PAP-immunostained sections showed that SST-28 (1-12), SST-14, and sSST-25 immunoreactivities occurred in the same cells. However, preabsorption tests demonstrated that anti-sSST-25 serum detected the invariant SST-14 molecule. The SST-28 (1-12)/SST-14-immunogold-labeled cells mainly had round or ovoid medium electron-dense granules. Glucagon-IR cells were characterized by round secretory granules with an electron-dense core, with or without a narrow clear halo. There were PP, PYY, and NPY (NPY-like) immunoreactivities in a population of glucagon-IR cells in the pancreatic duodenal region (glucagon/NPY cells). Most of the secretory granules of these glucagon/NPY-like cells had an electron-dense content and were round, although there were also pyriform or ovoid secretory granules which were smaller than those of glucagon-IR cells. Preabsorption tests proved that the NPY-like peptides detected in the endocrine pancreas of P. scripta elegans were more similar to NPY or PYY than to PP.
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PMID:Identification of the pancreatic endocrine cells of Pseudemys scripta elegans by immunogold labeling. 1064 38

Our understanding of the regulation of appetite and energy balance has advanced significantly over the past decade as several peptides, centrally or peripherally expressed, have been characterized and shown to profoundly influence food intake and energy expenditure. (1)The growing number of putative appetite-regulating neuropeptides includes peptides that are orexigenic (appetite-stimulating) signals and anorectic peptides. Neuropeptide Y (NPY), melanin concentrating hormone (MCH), orexins A and B, galanin, and agouti -related peptide (AgRP) all act to stimulate feeding while alpha-melanocyte stimulating hormone (alphaMSH), corticotropin releasing hormone (CRH), cholecystokinin (CCK), cocaine and amphetamine regulated transcript (CART), neurotensin, glucagon-like peptide 1 (GLP 1), and bombesin have anorectic actions.(1) Leptin, expressed in the periphery in white adipose tissue, acts in the CNS to modulate the expression of several of these hypothalamic peptides.(1) This creates a functional link between the adipose tissue and the brain that translates the information on body fat provided by leptin to input into energy balance regulating processes. In the current review we examine the significant role of the melanocortin system (alphaMSH, agouti and AgRP peptides, and their receptors and mahogany protein) and melanin concentrating hormone in the regulation of energy balance.
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PMID:Two important systems in energy homeostasis: melanocortins and melanin-concentrating hormone. 1065 11


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