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)

In this study, a selective antagonist of cholecystokinin (CCK)-A receptors, loxiglumide, was used to evaluate the role of CCK in the control of the release of gastrin and pancreatic hormones (insulin, glucagon, pancreatic polypeptide (PP), and somatostatin) after stimulation with exogenous CCK and ingestion of a standard liquid mixed meal in healthy humans. Exogenous CCK-8, which induced a small but significant increase in gastric acid secretion, resulted in dose-dependent increments in plasma PP levels without significant changes in plasma levels of insulin, glucagon, or somatostatin. Pretreatment with loxiglumide resulted in a marked increase in CCK-induced gastric acid secretion and abolished the increments in plasma PP without alteration of plasma insulin, glucagon, or somatostatin levels. Ingestion of the liquid meal resulted in an immediate rise in intragastric pH from basal values of about 2 to pH6 lasting 90-120 min, and this was accompanied by significant increments in plasma gastrin, insulin, glucagon, PP, and somatostatin. Administration of loxiglumide (1200 mg orally) caused a reduction in the postprandial intragastric pH and the two- to three-fold increase in plasma gastrin. Plasma insulin and glucagon levels in tests with loxiglumide tended to increase, probably owing to accelerated gastric emptying, whereas plasma PP and somatostatin were significantly reduced. This study provides evidence that CCK exerts an inhibitory effect on gastric acid secretion and plasma gastrin release as well as a stimulatory influence on the release of PP and somatostatin via CCK-A receptors but does not influence directly insulin or glucagon secretion in man.
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PMID:Cholecystokinin in the regulation of gastric acid and endocrine pancreatic secretion in humans. 851

Activation of type A receptors by CCK or cerulein is known to stimulate pancreatic enzyme secretion, but its role in the amino acid (AA) consumption and enzyme synthesis remains unclear. In our study, we used loxiglumide, a potent CCK-A-receptor antagonist, to investigate the role of CCK-A receptors in pancreatic consumption of circulating AAs and enzyme secretion. Five healthy male volunteers were intubated with double-lumen duodenal tube, and duodenal aspirates were collected during 60-min basal periods and then during pancreatic stimulation with iv infusion of secretion (80 pmol/kg/h) plus cerulein (50 pmol/kg/h) during three consecutive 30-min periods. The same procedure was repeated, but secretin-cerulein infusion was combined with a constant dose of loxiglumide (20 mumol/kg/h). The volume and outputs of HCO3-, protein and enzymes (amylase and trypsin) in duodenal aspirates and gallbladder volume (by sonography) were determined at 30-min intervals. Plasma samples were drawn for total plasma AA assay by ninhydrin method to assess the pancreatic uptake of free AAs. Infusion of secretin plus cerulein caused a several-fold increase in the volume of duodenal aspirate and the outputs of HCO3-, protein, and enzymes. During those periods, plasma AA level decreased from initially 2.20 +/- 0.3 mmol/L to 1.09 +/- 0.3 mmol/L (p < 0.01) and the gallbladder volume from initially 28 +/- 8 mL to 2 +/- 0.4 mL. This increase in pancreatic secretory outputs was accompanied by significant increments in plasma insulin, glucagon, PP, and somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholecystokinin (CCK) in the amino acid uptake and enzyme protein secretion by the pancreas in humans. 856 35

The effects of three C-terminal fragments of cholecystokinin (CCK) (CCK-8-sulphated form [SF], CCK-8-non-sulphated form [NSF] and CCK-4) on insulin and glucagon secretion were examined in sheep in vivo. Each CCK fragment was injected intravenously at a wide range of doses (1 pmol to 3 x 10(5) pmol kg-1). CCK-8(SF) had the lowest threshold dose (10 pmol kg-1) and a maximal response dose of 10(3) pmol kg-1 for increasing plasma insulin concentration; the respective threshold doses of CCK-8(NSF) and CCK-8 for increasing plasma insulin were 30 and 100 times greater than that of CCK-8(SF). A maximal insulin response was not obtained at the highest doses of CCK-8(NSF) or CCK-4 tested (3 x 10(3) and 3 x 10(5) pmol kg-1, respectively). These results indicate that CCK-A type receptors rather than CCK-B receptors may be involved in CCK-induced insulin secretion in sheep. None of the CCK fragments affected plasma glucagon concentration. The lack of a glucagon response to exogenous CCK-fragments may be one of the characteristics of the endocrine pancreatic responses of ruminant species.
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PMID:Effects of C-terminal fragments of cholecystokinin on plasma insulin and glucagon concentrations in sheep. 924 18

Intraduodenal fat inhibits gastric acid secretion via the release of one or more hormonal enterogastrones thought to arise from ileocolonic mucosa. This study determined whether glucagon-like peptide-1 (GLP-1)-(7-36) amide and peptide YY (PYY), colocalized in L cells found in the ileum, mediate intraduodenal fat-induced inhibition of stimulated gastric acid, and evaluated the influence of cholecystokinin-A (CCK-A) receptor activation. Gastric acid secretion in response to duodenal perfusions of 8% peptone was measured in conscious dogs with gastric and duodenal cannulas. Intraduodenal administration of a 10% fat emulsion suppressed gastric acid secretion by 72 +/- 4% (P < 0.001) and increased plasma levels of GLP-1 and PYY by 44 +/- 5 and 46 +/- 4 fmol/ml, respectively (both P < 0.01). Pretreatment with the CCK-A receptor antagonist MK-329 completely reversed the inhibition of gastric acid by fat, suppressed rises of plasma GLP-1 (maximum change, 23 +/- 4 fmol/ml), and reduced plasma PYY responses to baseline. Intravenous infusions of 50 pmol/kg x h GLP-1 or PYY, which reproduced plasma elevations after intraduodenal fat, inhibited gastric acid secretion by 66 +/- 5% and 51 +/- 6%, respectively (both P < 0.01); coinfusions of GLP-1 and PYY abolished gastric acid secretion (P < 0.001) without influencing plasma gastrin or somatostatin. Pretreatment with 1500 pmol/kg x h of the GLP-1 antagonist exendin-(9-39) amide did not alter the magnitude of inhibition of gastric acid caused by exogenous GLP-1. These results indicate that GLP-1 and PYY released by intraduodenal fat, in part through CCK-dependent pathways, are major enterogastrones in dogs. This inhibitory action occurs independent of circulating concentrations of somatostatin and gastrin and appears to involve a GLP-1 receptor distinct from that mediating incretin effects.
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PMID:Glucagon-like peptide-1-(7-36) amide and peptide YY mediate intraduodenal fat-induced inhibition of acid secretion in dogs. 942 14

Gastrin (G) and cholecystokinin (CCK) are gastrointestinal neuropeptides that are released into circulation during a meal. G is also transiently expressed during embryogenic and early ontogenic development of the pancreas and is believed to act on islet-cell development. Both peptides act on pancreatic endocrine function; however, the effects are dependent on the species and on cellular and molecular underlying mechanisms that remain poorly characterized. Since CCK-B/G subtype receptor is predominant over the CCK-A subtype in the human pancreas, we hypothesized that it could be expressed by islet cells. Here we present reverse transcription-polymerase chain reaction and immunohistochemistry data demonstrating that the CCK-B/G receptor is expressed in islet cells and that islet glucagon-producing cells are the major site of CCK-B/G receptor expression in adult and fetal pancreas. Moreover, G immunoreactivity was detected in the fetal human pancreas at embryogenic week 22. G- and CCK-stimulated glucagon are released from purified human islets. Concentration of CCK and G eliciting a half-maximal level of glucagon secretion were 13 +/- 6 and 8 +/- 5 pmol/l, respectively. Maximal glucagon secretion was achieved in the presence of 30 pmol/l peptides and was similar to that obtained in the presence of 10 mmol/l L-arginine (1.6 pmol x ml(-1) x 90 min(-1)). The nonpeptide antagonist of the CCK-B/G receptor, RPR-101048, fully inhibited CCK- and G-stimulated glucagon secretion at 100 nmol/l concentration. These data are consistent with the view that the CCK-B/G receptor is involved in glucose homeostasis in adult humans and mediates the autocrine effects of G on islet differentiation and growth in the fetal pancreas.
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PMID:Evidence for a functional role of the cholecystokinin-B/gastrin receptor in the human fetal and adult pancreas. 1051 67

Food intake is a regulated system. Afferent signals provide information to the central nervous system, which is the centre for the control of satiety or food seeking. Such signals can begin even before food is ingested through visual, auditory and olfactory stimuli. One of the recent interesting findings is the demonstration that there are selective fatty acid taste receptors on the tongue of rodents. The suppression of food intake by essential fatty acids infused into the stomach and the suppression of electrical signals in taste buds reflect activation of a K rectifier channel (K 1.5). In animals that become fat eating a high-fat diet the suppression of this current by linoleic acid is less than that in animals that are resistant to obesity induced by dietary fat. Inhibition of fatty acid oxidation with either mercaptoacetate (which blocks acetyl-CoA dehydrogenase) or methylpalmoxirate will increase food intake. When animals have a choice of food, mercaptoacetate stimulates the intake of protein and carbohydrate, but not fat. Afferent gut signals also signal satiety. The first of these gut signals to be identified was cholecystokinin (CCK). When CCK acts on CCK-A receptors in the gastrointestinal tract, food intake is suppressed. These signals are transmitted by the vagus nerve to the nucleus tractus solitarius and thence to higher centres including the lateral parabrachial nucleus, amygdala, and other sites. Rats that lack the CCK-A receptor become obese, but transgenic mice lacking CCK-A receptors do not become obese. CCK inhibits food intake in human subjects. Enterostatin, the pentapeptide produced when pancreatic colipase is cleaved in the gut, has been shown to reduce food intake. This peptide differs in its action from CCK by selectively reducing fat intake. Enterostatin reduces hunger ratings in human subjects. Bombesin and its human analogue, gastrin inhibitory peptide (also gastrin-insulin peptide), reduce food intake in obese and lean subjects. Animals lacking bombesin-3 receptor become obese, suggesting that this peptide may also be important. Circulating glucose concentrations show a dip before the onset of most meals in human subjects and rodents. When the glucose dip is prevented, the next meal is delayed. The dip in glucose is preceded by a rise in insulin, and stimulating insulin release will decrease circulating glucose and lead to food intake. Pyruvate and lactate inhibit food intake differently in animals that become obese compared with lean animals. Leptin released from fat cells is an important peripheral signal from fat stores which modulates food intake. Leptin deficiency or leptin receptor defects produce massive obesity. This peptide signals a variety of central mechanisms by acting on receptors in the arcuate nucleus and hypothalamus. Pancreatic hormones including glucagon, amylin and pancreatic polypeptide reduce food intake. Four pituitary peptides also modify food intake. Vasopressin decreases feeding. In contrast, injections of desacetyl melanocyte-stimulating hormone, growth hormone and prolactin are associated with increased food intake. Finally, there are a group of miscellaneous peptides that modulate feeding. beta-Casomorphin, a heptapeptide produced during the hydrolysis of casein, stimulates food intake in experimental animals. In contrast, the other peptides in this group, including calcitonin, apolipoprotein A-IV, the cyclized form of histidyl-proline, several cytokines and thyrotropin-releasing hormone, all decrease food intake. Many of these peptides act on gastrointestinal or hepatic receptors that relay messages to the brain via the afferent vagus nerve. As a group they provide a number of leads for potential drug development.
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PMID:Afferent signals regulating food intake. 1099 53

Cholecystokinin (CCK) plays a major role in the regulation of pancreatic enzyme secretion based on its binding to the CCK-A receptor (CCK-AR). While CCK-AR is known to be expressed in rat islet B cells, the localization of CCK-AR in rat pancreatic A and D cells remains poorly understood. The aim of this study was to identify the localization of CCK-AR in rat pancreatic islets by means of double immunofluorescence straining with antibodies against CCK-AR, glucagon, insulin and somatostatin and with in situ hybridization to detect its transcript. CCK-AR-like immunoreactive cells were found to overlap both with glucagon-like immunoreactive cells and insulin-like immunoreactive cells but not with somatostatin-like immunoreactive cells. An in situ hybridization study using a cRNA probe for CCK-AR revealed that CCK-AR mRNA was expressed in the center and periphery of the pancreatic islets. Further to this, immunofluorecsence staining using anti-glucagon antibody was carried out after in situ hybridization using the CCK-AR cRNA probe in order to identify CCK-AR mRNA expressing cells. CCK-AR mRNA exhibited a distribution pattern almost identical to that of glucagon-like immunoreactive cells. These results show clearly that CCK-AR exists not only in B but also in A cells of the rat pancreas, suggesting that CCK regulates the secretion of insulin and glucagon at least partly via CCK-AR.
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PMID:Immunohistochemical analysis of cholecystokinin A receptor distribution in the rat pancreas. 1562 Apr 27

We hypothesized that protein source in the nutritionally adequate AIN-93G diets fed during gestation, lactation, and weaning influences food intake (FI) regulation in male offspring of Wistar rats. Pregnant rats were fed the recommended casein-based (C) or soy protein-based (S) diet during gestation (experiment 1) or during gestation and lactation (experiment 2). Pups (n = 12 per group) weaned to C or S diets were followed for 9 wk (experiment 1) or 14 wk (experiment 2). At termination, body weight was 5.4% and 9.4% higher, respectively, in offspring of dams fed the S diet. Altered FI regulation was shown by failure of devazepide (a CCK-A receptor blocker) to block FI reduction after protein preloads in offspring of S diet-fed dams, whereas it had a strong effect on offspring of C diet-fed dams (P < 0.005). Similarly, naloxone (an opioid receptor blocker) blocked FI reduction more after casein than after soy protein preloads (P < 0.01). In experiment 2, offspring of dams fed the S diet had higher hypothalamic gene expression of agouti related protein at weaning (P < 0.05), and higher FI was found throughout postweaning (P < 0.0001). FI reduction after protein preloads at week 7 and after glucose preloads at week 13 was greater in offspring of C diet-fed dams (P < 0.05). Plasma insulin at weaning and insulin, ghrelin, and glucagon-like peptide-1 at week 15 were higher in offspring of S diet-fed dams (all P < 0.05). In conclusion, nutritionally complete C and S diets consumed during gestation and lactation differ in their effects on body weight and FI regulation in the offspring. Extending the diet from gestation alone to throughout gestation and lactation exaggerated the adverse effects of the S diet. However, the diet consumed postweaning had little effect on the outcome.
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PMID:Effect of protein source in diets fed during gestation and lactation on food intake regulation in male offspring of Wistar rats. 2132 47