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)

We have studied the effect of pig pancreastatin on glucose and lactate production in freshly isolated rat hepatocytes. Pancreastatin stimulated the rate of glucose output, whereas, in contrast with glucagon, it failed to modify the rate of lactate production. The effective concentration of pancreastatin was in the range 0.1-100 nM, with half-maximal rate close to 1 nM. The ability of pancreastatin to increase glucose output was abolished by chelation of the calcium in the medium. By itself, pancreastatin did not increase cyclic AMP (cAMP) levels and had no influence on cAMP levels in glucagon-stimulated hepatocytes. Our results point out a possible role of pancreastatin in glycogenolysis. This appears to be mediated by a cAMP-independent Ca(2+)-dependent mechanism.
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PMID:Glycogenolytic effect of pancreastatin in isolated rat hepatocytes is mediated by a cyclic-AMP-independent Ca(2+)-dependent mechanism. 137 10

1. Pancreastatin, a 49 amino acid peptide derived from chromogranin A, has been shown to have an inhibitory effect on insulin secretion in the perfused pancreas and isolated islets. 2. We have studied the effect of pancreastatin on glucagon-stimulated insulin release and the hyperglycemic of glucagon effect in vivo. 3. When administered in the mesenteric vein, pancreastatin inhibited the increase in insulin levels induced by glucagon stimulation, thereby potentiating the hyperglycemic effect of glucagon. 4. This study describes a regulatory role of pancreastatin on glucagon-induced insulin release in vivo.
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PMID:Pancreastatin and its 33-49 C-terminal fragment inhibit glucagon-stimulated insulin in vivo. 139 69

The identification of pancreastatin in pancreatic extracts prompted the investigation of its effects on islet cell function. However, in most of the investigations to date, pig pancreastatin was tested in heterologous species. Since there is great interspecies variability in the amino acid sequence of pancreastatin, we have investigated the influence of rat pancreastatin on insulin, glucagon and somatostatin secretion in a homologous animal model, namely the perfused rat pancreas. During 5.5 mM glucose infusion, pancreastatin (40 nM) inhibited insulin secretion (ca. 40%, P less than 0.025) as well as the insulin responses to 10 mM arginine (ca. 50%, P less than 0.025) and to 1 nM vasoactive intestinal polypeptide (ca. 50%; P less than 0.05). Pancreastatin failed to significantly modify glucagon or somatostatin release under any of the above experimental conditions. In addition, a lower pancreastatin concentration (15.7 nM) markedly suppressed the insulin release evoked by 11 mM glucose (ca. 85%, P less than 0.05). Our present observations reinforce the concept that pancreastatin is an effective inhibitor of insulin secretion, influencing the B-cell function directly and not through an A-cell or D-cell paracrine effect.
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PMID:Homologous pancreastatin inhibits insulin secretion without affecting glucagon and somatostatin release in the perfused rat pancreas. 168 69

Pancreastatin (PST), a peptide isolated from porcine pancreas in 1986, has been reported to inhibit insulin and to stimulate glucagon secretion. Since both of these effects have been questioned, we investigated the effect of PST (20, 200, or 2000 pM) on hormone release in the isolated perfused rat pancreas at different glucose levels (1.7, 5.5, 11.1, and 16.7 mM). At 1.7 mM glucose, 20 pM PST had no significant effect on glucagon secretion, whereas 200 pM and 2 nM PST significantly inhibited glucagon release. At a concentration of 5.5 mM glucose, insulin output was not affected by PST in any of the concentrations tested. At 11.1 mM glucose, however, 200 pM and 2 nM PST significantly inhibited insulin output. At 16.7 mM glucose, insulin secretion was significantly reduced by all concentrations of PST tested. Unstimulated exocrine pancreatic secretion was not affected by PST in any of the experimental settings. We conclude that PST inhibits glucagon and insulin secretion dose-dependently, and these effects apparently are glucose-dependent. PST does not influence basal exocrine pancreatic secretion in vitro.
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PMID:Glucose-dependent effects of pancreastatin on insulin and glucagon release. 174 28

Pancreastatin is a 49 amino acid peptide originally isolated from porcine pancreas on the basis of its C-terminal glycinamide as isolation criterion. It is derived by proteolytic processing from chromogranin A, an acidic protein component of secretory granules in endocrine and neuronal cells. The primary structures of human, porcine, bovine and rat pancreastatin have been determined on the protein or cDNA level and show 70% sequence homology. By immunocytochemistry, pancreastatin has been detected in the pituitary, adrenal gland, pancreas, CNS and throughout the gastrointestinal tract. In pancreatic islets, pancreastatin is co-localized with insulin, glucagon and somatostatin. The principle biological activities of this peptide are: inhibition of insulin release and of exocrine pancreatic secretion. These effects which can be assigned to the amidated C-terminal part of the molecule have been demonstrated in several species. Whether or not pancreastatin can be classified as a novel peptide hormone that under physiological conditions plays a role in the regulation of the endocrine and exocrine pancreas, is still a matter of controversy.
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PMID:Pancreastatin--a novel regulatory peptide? 185 1

The effects of porcine pancreastatin on insulin release stimulated by insulinotropic agents, glucagon, cholecystokinin-octapeptide (CCK-8), gastric inhibitory polypeptide (GIP) and L-arginine, were compared to those of bovine chromogranin A (CGA) using the isolated perfused rat pancreas. Pancreastatin significantly potentiated glucagon-stimulated insulin release (first phase: 12.5 +/- 0.9 ng/8 min; second phase: 34.5 +/- 1.6 ng/25 min in controls; 16.5 +/- 1.1 ng/8 min and 44.0 +/- 2.2 ng/25 min in pancreastatin group), whereas CGA was ineffective. The first phase of L-arginine-stimulated insulin release was also potentiated by pancreastatin (6.9 +/- 0.5 ng/5 min in controls, 8.4 +/- 0.6 ng/5 min in pancreastatin group), but not by CGA. Pancreastatin did not affect CCK-8 or GIP-stimulated insulin release. Similarly, CGA did not affect insulin release stimulated by CCK-8 or GIP. These findings suggest that pancreastatin stimulates insulin release in the presence of glucagon. Because pancreastatin can have multiple effects on insulin release, which are dependent upon the local concentration of insulin effectors, pancreastatin may participate in the fine tuning of insulin release from B cells.
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PMID:Effects of pancreastatin and chromogranin A on insulin release stimulated by various insulinotropic agents. 185 78

We investigated the effects of porcine pancreastatin on the endocrine and unstimulated exocrine secretion of isolated, perfused porcine pancreas. Pancreastatin in a concentration of 10(-8) mol/l had no effect on basal secretion of insulin, glucagon and somatostatin at a perfusate glucose concentration of 5 mmol/l (n = 4) and neither at 10(-8) nor 10(-7) mol/l influenced the hormone responses to acute elevations of perfusate glucose concentration from 3.5 to 11 mmol/l (n = 7). This elevation strongly stimulated insulin secretion and inhibited glucagon secretion. Exocrine secretion was not affected by pancreastatin. The results suggest that pancreastatin does not directly influence pancreatic secretion.
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PMID:Porcine pancreastatin has no effect on endocrine secretion from the pig pancreas. 197 2

Pancreastatin is a 49 amino acid comprising peptide isolated from porcine pancreas that is derived by proteolytic processing from chromogranin A. Using an antibody against the synthetic C-terminal fragment pancreastatin (33-49), we examined the light and electron microscopical immunocytochemical localization of this peptide in porcine tissues. Pancreastatin-like immunoreactivity (PLI) was found in pancreatic somatostatin-, insulin- and glucagon cells in varying intensities; pancreatic polypeptide cells were always negative. At the electron microscopical (EM) level the immunoreactivity was confined to the electron dense core of the secretory granules in the case of somatostatin and insulin cells or to the less electron dense "halo" of the glucagon granules. In the antrum PLI positive cells represented gastrin (G), somatostatin (D) and enterochromaffin (EC) cells, in the duodenum in addition to EC- and G-cells a small number of PLI positive cells showed a positive immunoreaction for glucagon-like peptide (GLP) I and secretin in serial sections. Both norepinephrine and epinephrine containing cells of the adrenal medulla exhibited a strong reaction for PLI. In the pituitary several cell populations stained with varying intensities, including gonadotrophs and thyrotrophys. PLI is present in a distinct and characteristic subpopulation of neuroendocrine cells in various organs. The subcellular localization may indicate a function in the granular concentration, packaging and storage of peptides and amines in the brain-gut endocrine system.
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PMID:Light and electron microscopical immunocytochemical localization of pancreastatin-like immunoreactivity in porcine tissues. 218 73

Pancreastatin is a novel 49-amino acid peptide with a C-terminal glycine amide. The peptide was isolated from porcine pancreatic extracts and shows a structural similarity to chromogranin A. The effect of synthetic porcine pancreastatin on blood glucose levels and hepatic glycogen content was investigated in rats in vivo. Pancreastatin (300 pmol/kg) produced a time-dependent decrease in glycogen content of liver and a slight hyperglycemia. Basal plasma insulin and glucagon levels were not modified by pancreastatin. We suggest that pancreastatin could play a biological role in the glucose metabolism through a glycogenolytic effect.
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PMID:Glycogenolytic effect of pancreastatin in the rat. 218 44

Pancreastatin is a 49-amino acid straight chain molecule isolated from porcine pancreatic extracts. In the perfused rat pancreas, this peptide has been shown to inhibit unstimulated insulin release and the insulin responses to glucose, arginine, and tolbutamide. To further explore the influence of pancreastatin on islet cell secretion, the effect of synthetic porcine pancreastatin (a 2-micrograms priming dose, followed by constant infusion at a concentration of 15.7 nmol/L) was studied on the insulin, glucagon, and somatostatin responses to 1 nmol/L vasoactive intestinal peptide (VIP), 1 nmol/L gastric inhibitory peptide (GIP), and 1 nmol/L 26 to 33 octapeptide form of cholecystokinin (8-CCK). The effect of pancreastatin on the insulin and somatostatin secretion elicited by glucagon (20 nmol/L) was also examined. Pancreastatin infusion consistently reduced the insulin responses to VIP, GIP, and 8-CCK without modifying glucagon or somatostatin release. It also inhibited the insulin release but not the somatostatin output induced by glucagon. These observations broaden the spectrum of pancreastatin as an inhibitor of insulin release. The finding that pancreastatin does not alter glucagon or somatostatin secretion supports the concept that it influences the B cell directly, and not through an A cell or D cell paracrine effect.
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PMID:Pancreastatin inhibits insulin secretion as induced by glucagon, vasoactive intestinal peptide, gastric inhibitory peptide, and 8-cholecystokinin in the perfused rat pancreas. 266 67


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