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)

Gluconeogenesis from lactate, pyruvate, fructose, alanine, and other substrates was accelerated by glucagon or epinephrine in hepatocytes isolated from rat liver. Glucagon and epinephrine also increased cyclic AMP accumulation by rat hepatocytes. Isoproterenol increased cyclic AMP but not gluconeogenesis, while phenylephrine accelerated gluconeogenesis. The activation of gluconeogenesis by epinephrine was unaffected by propranolol but blocked by dihydroergotamine. Dibutyryl cyclic AMP added to hepatocytes stimulated gluconeogenesis at concentrations as low as 1 muM. Exogenous cyclic GMP (0.1- muM) inhibited gluconeogenesis due to either glucagon or epinephrine without affecting basal gluconeogenesis. However, carbamylcholine did not affect gluconeogenesis by hepatocytes. Basal gluconeogenesis and the increases due to all agents were inhibited by removal of extracellular calcium or the presence of A-23187, D-600, or tetracaine. In contrast, added 0.1 muM cyclic GMP, 2 mM NH-4-Cl, and 10 muM phenethylbiguanide inhibited glucagon- or epinephrine-stimulated gluconeogenesis without affecting basal values. Studies with hepatocytes indicate that the hormonal activation of gluconeogenesis is not limited to substrates entering prior to triose phosphate formation. Glucagon may act by increasing cyclic AMP which acts via unknown mechanisms to increase gluconeogenesis. In contrast, epinephrine acts via a cyclic AMP-independent mechamism which does not appear to involve cyclic GMP, Ca-2+ flux, of K+ flux.
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PMID:Cyclic nucleotides and gluconeogenesis by rat liver cells. 16 60

1. Isolated cat kidneys were perfused in situ with Locke solution and renin release in response to isoprenaline was studied. 2. Perfusion with isoprenaline produced a concentration-dependent enhancement of renin secretion. Increasing the concentration of stimulant also prolonged the duration of the secretory response. 3. After a 10 min exposure to isoprenaline (0-3 micrometer), there was a rapid facilitation of renin release which diminished after 10-30 min, followed by a second transient increase which declined over the next 40-60 min. Cycloheximide did not prevent augmented release when added together with the isoprenaline but did produce a reversible inhibition of the late phase when added 10 min after the isoprenaline. 4. Omission of calcium from the perfusion medium failed to depress the renin release induced by isoprenaline, glucagon, or furosemide. However, during prolonged calcium deprivation, the cycloheximide-sensitive phase of isoprenaline-evoked release was depressed. 5. The calcium antagonist D-600 failed to block the early phase of isoprenaline-induced renin secretion but inhibited the late phase of secretion. 6. Calcium alone elicited an explosive discharge of renin when added after a prolonged period of calcium-free perfusion. 7. These results support the view that extracellular calcium does not play an essential role in the mechanism of renin secretion from the renal juxtaglomerular cells, but that an increased influx of this cation is needed for synthesis and/or mobilization of the enzyme. It is tentatively proposed that the release of calcium from intracellular storage sites may be the signal which triggers renin secretion.
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PMID:The role of calcium in renin secretion from the isolated perfused cat kidney. 89 93

Regulation of insulin release and transmembrane Ca2+ fluxes was examined using pieces of 3 benign medullary-type insulinomas removed from the pancreas of female patients at surgery. Immunocytochemical staining confirmed the presence of insulin-containing cells with no demonstrable glucagon, somatostatin or pancreatic polypeptide. After 3 days of culture in RPMI-1640, tumour pieces released 11-158 mg insulin kg-1 dry wt during acute 60 min incubations with the concomitant uptake of 2-47 mmol 45Ca kg-1 into the intracellular lanthanum-nondisplaceable pool. At 2.56 mM Ca2+, glucose alone or in combination with glyceraldehyde, mannoheptulose or diazoxide did not modify insulin release or 45Ca uptake. Theophylline significantly increased insulin release from 2 tumours with a small stimulatory effect on the third. A depolarising concentration of K+ enhanced insulin release from one tumour but this was not associated with an increase of 45Ca uptake. Calcium antagonists, (verapamil, D-600 and trifluoroperazine) and calcium ionophores (A23187 and Br-X537A) failed to modify insulin release or 45Ca uptake by each of the two tumours tested. Evaluation of 45Ca efflux from one tumour confirmed the unresponsiveness to glucose, K+, verapamil and A23187. Prolonged culture of 2 tumours for up to 16 days was associated with the gradual decline of insulin release to a steady output of 2-15 ng 24 h-1. Addition of verapamil to the cultures inhibited insulin output from one tumour, but mannoheptulose or diazoxide were without effect. The results indicate that inappropriate insulin release from these 3 benign medullary-type insulinomas is associated with disturbances in the regulation of transmembrane Ca2+ fluxes.
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PMID:Defective regulation of insulin release and transmembrane Ca2+ fluxes by human islet cell tumours. 282 49

Isolated tissues from rat and guinea pig hearts were employed to investigate the relationship between the positive inotropic effects of isoproterenol and glucagon and the shortening of time to peak tension (TPT). The involvement of cAMP in the inotropic responses to histamine and isoproterenol and corresponding changes in TPT was also studied. On isoproterenol challenge, a correlation was found between the percent increase in tension and reduction in TPT. Histamine produced a positive inotropic response in both guinea pig left atria and papillary muscles; however, TPT was shortened only in the cAMP-associated response of the papillary muscle. In guinea pig left atria, isoproterenol in the absence and presence of D-600, RO-20-1724, or propranolol increased tissue levels of cAMP and decreased TPT such that a significant correlation was found between these two parameters. The significance of relationships among positive inotropic responses, tissue levels of cAMP, and TPT is discussed.
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PMID:Inotropic responses, cyclic AMP, and time to peak tension in isolated cardiac preparations. 630 91

Glucagon like peptide-1(7-36) amide (GLP-1(7-36)amide) stimulates both insulin secretion and the efflux of 45Ca2+ from 45Ca(2+)-preloaded rat islets in a Na(+)-dependent manner. This indicates that the peptide stimulates insulin secretion by Na(+)-dependently increasing the intracellular concentration of Ca2+ ([Ca2+]IC). However, whether GLP-1(7-36)amide actually affects the [Ca2+]IC in islet cells is not known. We therefore preloaded rat islet cells with the Ca(2+)-fluorophor fura 2-AM and examined the [Ca2+]IC in spectrophotofluorometry. We found that GLP-1(7-36)amide increased [Ca2+]IC both at 3.3 and 8.3 mM glucose but only in a medium containing both Ca2+ and Na+. Also the adenylate cyclase activator, forskolin (2.5 microM), increased the [Ca2+]IC but this action was evidenced also in the absence of extracellular Na+. Furthermore, the Ca(2+)-channel inhibitor, D-600 (50 microM), prevented the rise in [Ca2+]IC after both forskolin and GLP-1(7-36)amide, whereas pertussis toxin had no effect. The results show that GLP-1(7-36)amide increases the [Ca2+]IC in islets cells by an action that most likely is due to uptake of extracellular Ca2+ by a Na(+)-dependent mechanism, whereas forskolin increases [Ca2+]IC independently on Na+. It is hypothesized that GLP-1(7-36)amide stimulates a Na(+)-dependent step prior to the catalytic unit of the adenylate cyclase complex in islet cells.
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PMID:Effects of glucagon like peptide-1(7-36) amide on the cytoplasmic Ca(2+)-concentration in rat islet cells. 827 43