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)

The effects of the gastrointestinal hormone and neurotransmitter cholecystokinin (CCK8) are complex, since it exhibits both an insulinotropic and a glucagonotropic effect. We investigated CCK8 in vivo with respect to glucose fluxes (production and elimination) at both low (6 mM) and high plasma glucose levels (9 mM) using the primed constant D-[3-3H]glucose infusion technique. In the presence of high glucose levels there was a dose-dependent increase in glucose elimination by CCK8. No effect of CCK8 on glucose production at a high glucose infusion rate (500 mg/kg per h) was observed in contrast to a low glucose infusion rate (100 mg/kg per h); plasma glucagon levels were elevated. All effects on glucose production and elimination were specific, since they were abolished by the CCK receptor antagonist L-364,718. In summary, glucose elimination was slightly increased by CCK8 at low glucose levels but increased to a greater extent at high glucose levels; glucose production was increased by CCK8 only at low glucose levels. Thus, CCK is a regulator of glucose homeostasis.
 ...
PMID:The role of cholecystokinin (CCK8) on glucose production and elimination, and on plasma insulin and glucose in rats. 149 91

Duplex ultrasound was used to investigate superior mesenteric artery haemodynamics in humans in order to determine the physiological importance of postprandial blood concentrations of cholecystokinin octapeptide (CCK8), gastrin 17, secretin, and glucagon and to study whether a nervous cholinergic reflex mechanism has a role in the postprandial mesenteric blood flow response. Duplex parameters of vessel diameter, mean velocity, and flow volume were determined serially in the basal state and after stimulation. Changes were compared with baseline values. Superior mesenteric artery parameters were significantly increased over baseline values after a liquid test meal, but ingestion of saline did not cause any changes. Hormones infused simultaneously at postprandial concentrations did not change mesenteric blood flow. When they were infused at pharmacological doses, however, a significant increase in flow parameters was observed. Pretreatment with atropine significantly (p less than 0.05) reduced the mesenteric blood flow response to meal stimulation (57%). These data suggest that the four hormones tested are not of quantitative importance in regulating postprandial superior mesenteric artery blood flow. A cholinergic nervous reflex, however, participates in the control of food induced mesenteric artery flow changes.
 ...
PMID:Regulation of postprandial mesenteric blood flow in humans: evidence for a cholinergic nervous reflex. 175 82

Isolation of pure acinar cells of the rat pancreas was achieved employing counterflow sedimentation filtration technique (CSFT). The preparation of purified acinar cells contained an occasional red blood cell (RBC, 200:1) with total absence of endocrine and duct cells. A significant stimulation of amylase secretion from isolated pure acinar cells was produced by octapeptide of cholecystokinin (CCK8) and insulin produced potentiation of the effect of CCK8. Synthetic glucagon inhibited basal and CCK8 stimulated amylase secretion. Non-synthetic purified glucagon stimulated amylase secretion and potentiated the effect of CCK8. Vasoactive intestinal polypeptide (VIP) did not stimulate amylase secretion but potentiated the effect of CCK8. No leakage of lactic dehydrogenase (LDH) was detected from the cells in any of the secretion studies. Thus a highly purified preparation of isolated pure acinar cells of rat pancreas could be obtained with excellent morphologic and functional integrity.
 ...
PMID:Amylase secretion from isolated pure acinar cells. 240 20

The effect of CCK8 on glucagon, insulin and somatostatin release and its interaction with glucose was studied in freshly isolated rat pancreatic islets. While glucose alone inhibited glucagon secretion [half-maximal effect (EC50) = 4.6 mM], glucose in the presence of 10 nM CCK8 increased glucagon release (EC50 = 6.9 mM). This effect of CCK8 was dose-dependent at 11.1 mM glucose (EC50 = 1.0 nM). The dose-response curve for glucose on insulin secretion was shifted to the left by 10 nM CCK8; the EC50 of glucose was 11.6 and 9.3 mM in the absence and presence of CCK8, respectively. Glucose alone enhanced somatostatin release; this glucose-induced release was further increased by 10 nM CCK8. Our data indicate that first, CCK8 is able to reverse the inhibitory effect of glucose on glucagon secretion, second, CCK8 sensitizes the beta cell to the insulinotropic effect of glucose, and third, CCK8 enhances the effect of glucose on somatostatin release.
 ...
PMID:Cholecystokinin (CCK8) regulates glucagon, insulin, and somatostatin secretion from isolated rat pancreatic islets: interaction with glucose. 289 Nov 2

The selective binding of somatostatin-28 (SS-28) to beta cells of hamster insulinoma was characterized using HPLC-purified 125I-[Leu8,D-Trp22,Tyr25]SS-28 or 125I-SS-28. A single class of high-affinity sites (Kd = 53 +/- 5 pM) was observed with a binding capacity of 2.85 pmol/mg membrane protein. A large number of relatively low-affinity sites was found also. The order of potency of different peptides to inhibit 125I-SS-28 binding is SS-28 greater than SS-14 greater than SMS-201-995 and the respective half-maximal inhibitory doses are 0.16 nM, 10 nM and 1000 nM. CCK8 and other active pancreatic peptides (glucagon, insulin, gastric inhibitory peptide, vasoactive intestinal peptide, oxyntomodulin) do not inhibit the SS-28 receptor binding. 125I-SS-28-labeled beta membranes were successfully cross-linked using either the cleavable cross-linker dithiobis(succinimidylpropionate) (1 mM) alone or with a heterobifunctional agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB). In both cases five molecular components were revealed, after polyacrylamide gel electrophoresis of the membrane proteins and autoradiography, with the following molecular mass: 196-kDa, 132 kDa, 69 kDa, 45 kDa and 28 kDa. The labeling of 196-kDa, 132-kDa and 45-kDa species was specific in that they could be inhibited by unlabeled SS-28. The major labeled species corresponds to the 132-kDa band and no change in the mobility of this HSAB covalently bound SS-28 receptor was found after addition of dithiothreitol, suggesting that this specific receptor does not contain interchain disulphide bonds. The molecular mass of SS-28 receptors differs markedly from that of guinea-pig pancreatic acinar membranes, where a single 93-kDa protein is identified as a 125I-SS-28 receptor site in comparative experiments. Both the binding kinetics and structural differences sustain the selective action of SS-28 in the endocrine pancreas.
 ...
PMID:Characterization of covalently cross-linked somatostatin receptors in hamster beta cell insulinoma. 289 92

Cholecystokinin-8 (CCK-8) was injected into the lateral cerebral ventricles (LV) of conscious sheep to determine its effect on secretion of three hormones important in regulation of peripheral metabolism: growth hormone (GH), glucagon, and insulin. Three hr continuous LV injection of 0.64 pmol/min CCK-8 decreased plasma insulin concentration approximately 30% throughout the three hr period, compared to control injection, and this effect occurred independently of whether or not the sheep were permitted to eat during injection. Only high doses of desulfated CCK-8 affected plasma insulin levels, thus suggesting the involvement of specific CCK receptors. Plasma glucose and GH concentrations were unaffected by LV injections, but plasma glucagon concentration was also decreased by CCK-8. LV injection of 0.64 pmol/min CCK-8 in sheep given an IV bolus injection of glucose (1.0 g/kg body mass) resulted in significantly lower plasma insulin and higher plasma glucose concentrations than during control LV injections; thus CCK-8 is capable of suppressing insulin secretion even under stimulated conditions. Since cisterna magna injections of CCK-8 were not effective in suppressing insulin secretion, more rostral brain sites are probably responsible for mediating this effect.
 ...
PMID:CCK-octapeptide injected into cerebral ventricles of sheep decreases plasma insulin level. 388 48

The effects of cholecystokinins (CCK), caerulein, bombesin 6-14 nonapeptide (bombesin), and physalaemin on gastric secretion in Styela clava were measured using a perfusion technique. Varying concentrations of both CCK33 and CCK8 produced a significant dose-dependent response. Dose for dose, CCK33 was more potent than CCK8, while the assay was unable to show any discrimination between sulphated and nonsulphated forms of CCK8. The specific CCK inhibitor Bt2cGMP significantly reduced the response to both CCK33 and CCK8. Both caerulein and physalaemin were effective although with a considerably reduced response compared with CCK. Bombesin was the most potent of all secretagogues tested while glucagon was without effect on gastric secretion. It is suggested that the primitive prepancreatic zymogen cells in Styela possess a receptor or receptors with an ability to recognize those peptides which are also active on vertebrate pancreatic acinar cells. It is further suggested that while the results indicate a receptor system less sophisticated than that found in vertebrates, they also imply the presence of an endogenous polypeptide hormone or hormones with a sequence which might be expected to show similarities to more than one vertebrate gastrointestinal peptide.
 ...
PMID:Comparative studies on the effects of cholecystokinins, caerulein, bombesin 6-14 nonapeptide, and physalaemin on gastric secretion in the ascidian Styela clava. 609 Feb 64

Previously, we reported that pancreatic acini have specific receptors for the insulin-like growth factors (IGF) I and II. We now report that the binding of 125I-labeled IGF II to mouse pancreatic acini is maximally increased by 100 nM insulin (51%) and is maximally reduced by 10 nM cholecystokinin octapeptide (CCK8) (34%), but is not affected by other regulatory peptides such as somatostatin or glucagon. Since many polypeptide hormones are internalized, we determined whether this regulation of IGF II binding occurred via a change in internalization. Acid washing or trypsinization has been shown to remove surface-bound hormone while the acid- or trypsin-resistant radioactivity represents internalized radioligand. Insulin increased and CCK8 decreased the internalization of IGF II as determined by these techniques. Studies of IGF II binding to acini at low temperature (15 degrees C) and binding to particulate fractions from acini were also consistent with the effect of insulin to increase and CCK8 to decrease the internalization of IGF II. When insulin and CCK8 were added together, the inhibitory effect of CCK8 predominated, indicating that CCK8 acted distal to the effect of insulin. Several lines of evidence suggest that this effect of CCK8 was via the CCK receptor and was mediated via a change in intracellular Ca2+: the effect of CCK8 on inhibiting IGF II binding was blocked by the cholecystokinin antagonist N2,O2'-dibutyryl cGMP; the cholinergic agent carbachol (1-100 microM), which acts through the muscarinic receptor to increase intracellular Ca2+, also inhibited IGF II binding; the Ca2+ ionophore A23187 (1-5 microM) mimicked the effects of CCK8 and carbachol. These data indicate, therefore, that CCK8 and possibly insulin may regulate the internalization of IGF II via intracellular Ca2+. Moreover, the data raise the possibility that alterations of hormone internalization may be a general phenomenon of hormone-hormone interaction.
 ...
PMID:Effect of intracellular Ca2+ on insulin-like growth factor II. internalization into pancreatic acini. Roles of insulin and cholecystokinin. 609 32

In the present study, the effects of experimental lead pollution on gut endocrine cells have been determined in the goldfish Carassius carassius (L.) var.auratus by immunocytochemical reactions. In the mucosa and submucosa, only vasoactive intestinal polypeptide- and 5-HT-like immunoreactive nerve fibers were observed. Endocrine cells displaying immunoreactivity against gastrin, CCK8, metenkephalin, bombesin, neuropeptide Y, pancreatic polypeptide, substance P, secretin, somatostatin and vasoactive intestinal polypeptide antibodies were detected. No immunoreactivity against glucagon, insulin and 5-HT antibodies was revealed in the endocrine cells. Some modifications appeared evident in the endocrine cells 48-96 h after lead intoxication, and can be summarized as follows: 1) discharge of secretory granules (secretin- and vasoactive intestinal polypeptide-like peptides), up to the extent that the cells appeared to be depleted of secretory material; 2) increase of immunoreactivity in the endocrine cells (met-enkephalin- and pancreatic polypeptide-like peptides) or in the frequency of positive cells (met-enkephalin-like peptide); 3) no variations (gastrin-, CCK8, bombesin-, somatostatin- and substance P-like peptides). The alterations were not enhanced by long term treatment. Nerve fibers did not show modifications.
 ...
PMID:Immunocytochemical study of endocrine cells in the gut of goldfish Carassius carassius (L.) var. auratus submitted to experimental lead intoxication. 911 38

Glicentin (GLIC), oxyntomodulin (OXM), and peptide YY (PYY) released in blood by ileocolonic L-cells after meals may inhibit pancreatic secretion. Whereas OXM interacts with glucagon and tGLP-1 receptors, OXM 19-37, a biologically active fragment, does not. The purpose of this study was to measure the effect of OXM, OXM 19-37, GLIC, tGLP-1, and PYY on pancreatic secretion stimulated by 2 deoxyglucose (2DG), electrical stimulation of the vagus nerves (VES), acetylcholine and cholecystokinin octapeptide (CCK8) in anesthetized rats. The effect of OXM was also studied in dispersed pancreatic acini. Plasma oxyntomodulin-like immunoreactivity (OLI) was measured by radioimmunoassay after the exogenous infusion of OXM and after an intraduodenal meal. OXM 19-37, infused at doses mimicking postprandial plasma levels of OLI, decreased pancreatic secretion stimulated by 2DG, VES, or CCK8. Similar effects were found with OXM and GLIC. OXM 19-37 did not change the pancreatic stimulation induced by acetylcholine in vivo, or CCK-induced amylase release in isolated acini. Vagotomy completely suppressed the inhibitory effect of OXM 19-37 on CCK8-stimulated pancreatic secretion. PYY inhibited the effect of 2DG, but not that of CCK8, whereas tGLP-1, even in pharmacologic doses, had no effect on stimulated pancreatic secretion. OXM, OXM 19-37, but not tGLP-1, inhibit pancreatic secretion at physiologic doses, through a vagal neural indirect mechanism, different from that used by PYY, and probably through a GLIC-related peptide-specific receptor.
 ...
PMID:Oxyntomodulin inhibits pancreatic secretion through the nervous system in rats. 1082 88


1 2 Next >>