Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthetic analogues of CCK-4 in which Trp was replaced by D-Pro (peptide I), Thz (peptide II) and delta Pro (peptide III) have been studied for their insulin and glucagon releasing activities from the islets of Langerhans in vitro. Peptide I has been found to be the most potent insulin releaser among the three analogues and its activity is comparable to that of CCK-4. Unlike CCK-4, its three analogues (peptides I-III) do not stimulate the release of glucagon with basal concentration of glucose in the medium. However, with increasing glucose concentration, all the three analogues potentiate the glucose stimulus for insulin release.
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PMID:Selective stimulation of insulin secretion by CCK-4 analogues having N-terminal modifications. 186 88

The biologic activities of three synthetic analogues of CCK-4 (Trp-Met-Asp-Phe-NH2) in which (i) the C-terminal residue Phe was N-methylated (peptide I); (ii) the C-terminal Phe residue was N-methylated and Ser is substituted for Met in position 2 (peptide II); (iii) Pro was substituted for Trp in position 1 and the C-terminal amino nitrogen was methylated (peptide III), have been described. Peptides I and II have been found to inhibit the release of both insulin and glucagon, while peptide III was found to be a potent releasing agent for insulin and an inhibitor for glucagon.
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PMID:Effect of some novel synthetic analogues of CCK-4 on insulin and glucagon secretion. 269 15

It is known that cholecystokinin (CCK) stimulates islet hormone secretion under a variety of experimental conditions. Since CCK occurs in several different molecular forms, with 58, 39, 33, 12, 8, or 4 amino acid residues, the question has evolved as to which is the shortest active form of CCK. We therefore investigated the influences of the C-terminal octapeptide of CCK, CCK-8 (sulfated form) and of the C-terminal tetrapeptide, CCK-4, on the secretion of insulin, glucagon, and somatostatin from the pig pancreas in vivo by infusing each of the two peptides into the superior pancreatic artery. We found that islet hormone secretion increased promptly upon infusion of both CCK-8 and CCK-4. Thus, the secretion of insulin was stimulated from 51 +/- 12 to 295 +/- 70 microU/min during the first 2 min after injection of CCK-8 and from 40 +/- 12 to 240 +/- 78 microU/min after injection of CCK-4. Similarly, the secretion of glucagon was stimulated from 240 +/- 45 to 357 +/- 38 pg/min after CCK-8 and from 282 +/- 44 to 335 +/- 43 pg/min after CCK-4, and somatostatin secretion was stimulated from 112 +/- 7 to 226 +/- 12 pg/min by CCK-8 and from 105 +/- 11 to 246 +/- 16 pg/min by CCK-4. With regard to the efficiency to stimulate the secretion of these three islet hormones, CCK-8 and CCK-4 were equipotent. We conclude that in pigs, CCK-8 and CCK-4 both stimulate the secretion of insulin, glucagon, and somatostatin from the pancreas in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholecystokinin (CCK)-4 and CCK-8 stimulate islet hormone secretion in vivo in the pig. 289 79

Two synthetic analogs of CCK-4, Glp-Met-Asp-Phe-NH2 (I) and Pro-Met-Asp-Phe-NH2 (II) reported earlier to stimulate insulin release from the isolated rat pancreatic islets in vitro at concentrations as low as 10(-10) M, have now been found to be totally ineffective as glucagon releasers at concentrations as high as 10(-6) M or higher. It is evident that the replacement of Trp in CCK-4 by Glp and Pro residues leads to peptides which exhibit insulin releasing activity without stimulating the release of glucagon.
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PMID:Synthetic analogs of cholecystokinin terminal tetrapeptide that stimulate insulin but not glucagon release from pancreatic islets. 353 37

The effect of cholecystokinin (CCK)-4, nonsulfated CCK-8 (CCK-8), and sulfated CCK-8 (CCK-8-S) on endocrine pancreas function was investigated in the isolated perfused dog pancreas in the presence of 5.5 mM glucose. CCK-4 and CCK-8 at concentrations of 1, 10, and 100 nM dose dependently stimulated pancreatic SRIF, insulin, and glucagon release. The insulinotropic and glucagonotropic potency of CCK-8 was significantly greater than that of CCK-4, whereas the effect on SRIF secretion was similar. Furthermore, CCK-8-S and CCK-8 at concentrations of 0.1, 1, and 10 nM caused a dose-dependent increase in pancreatic A, B, and D cell secretion. The CCK-8-S was a more potent insulinotropic agent than CCK-8. It is suggested that these principal molecular CCK forms qualify for a physiological modulatory role in the endocrine pancreas.
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PMID:Effects of cholecystokinin (CCK)-4, nonsulfated CCK-8, and sulfated CCK-8 on pancreatic somatostatin, insulin, and glucagon secretion in the dog: studies in vitro. 614 59

A study was made of the action of C-terminal tetrapeptide cholecystokinin (CCK-4) on the secretory function of A-, B- and D-cells of the islets of Langerhans and on the lactotropic function of the hypophysis. Intravenous injection into rats of CCK-4 in doses of 5 and 50 micrograms/kg bw resulted within 2 min in increased blood immunoreactive insulin. Tetrapeptide also exerted a stimulant dose-dependent action on the function of insulin-, glucagon- and somatostatin-secreting pancreatic cells of the pancreatic islets in culture at concentrations ranging within 10(-9)-10(-6)M. When given in the same doses CCK-4 did not affect basal or dopamine-inhibited prolactin secretion by cultured adenohypophyseal cells. It is concluded that CCK-4 stimulates insulin, glucagon and somatostatin secretion by direct contact with target cells.
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PMID:[Effect of C-terminal tetrapeptide cholecystokinin (CCK-4) on the function of the islands of Langerhans and the adenohypophysis]. 614 60

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

Endocrine cells containing gastrin/cholecystokinin (CCK)-like immunoreactivity were localized to the islet tissue in the pancreas of the spiny dogfish. Most of these cells were located in the 'intestinal' lobe of the pancreas; only occasional cells were observed in the 'splenic' lobe. The gastrin/CCK-like immunoreactive cells were often co-localized with the 'classical' pancreas hormones (insulin, glucagon and somatostatin). Radioimmunoassay of water extracts with a C-terminally directed antiserum revealed high levels of immunoreactive material in the intestinal part (48.6 +/- 19.9 pmol/g) and lower levels (4.5 +/- 0.6 pmol/g) in the splenic part. Acetic acid extracts of the intestinal lobe contained low levels (6.8 +/- 3.3 pmol/g) of gastrin/CCK-like immunoreactivity, whereas corresponding extracts of the splenic part showed no immunoreactivity. When the extracts were subjected to DEAE ion-exchange chromatography the gastrin/CCK-like peptides eluted as a major peak. After Sephadex gel filtration, pooled immunoreactive material from the main DEAE chromatographic peak eluted at a position close to that of CCK4. Further characterization by ion-exchange and reversed-phase HPLC showed that, in general, the immunoreactive material behaved like the shorter forms of the gastrin/CCK family (CCK4/G5 and CCK8/Cae 3-10).
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PMID:Endocrine cells with gastrin/cholecystokinin-like immunoreactivity in the pancreas of the spiny dogfish, Squalus acanthias. 1250 16