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)

Although glucagon exerts positive inotropic effects in patients with no or mild impairment of cardiac function, similar effects are not consistently observed in patients with chronic heart failure. Accordingly, the inotropic effects of glucagon on papillary muscles from normal cats and cats in which right ventricular failure had been produced for 4-145 days by pulmonary artery banding were compared. At the peak of the concentration-response curve, glucagon increased peak isometric tension (T) in normal muscles from 4.4+/-0.4 to 6.6+/-0.5 g/mm(2) (P <0.001), and maximum rate of tension development (dT/dt) from 16.9+/-0.9 to 25.1+/-1.6 g/sec per mm(2) (P < 0.001). In contrast, glucagon produced no significant increases in T or dT/dt in failure muscles. The percentage increases in T and dT/dt caused by norepinephrine were the same in muscles from normal and failing hearts. Since the cardiac effects of glucagon and norepinephrine may be mediated by adenyl cyclase, responsiveness of adenyl cyclase was determined in particulate fractions of the right ventricle. Glucagon activated adenyl cyclase in normal, but had no effect in failure preparations. Norepinephrine-induced activation of adenyl cyclase, however, was unaltered by failure. Thus, in contrast to norepinephrine, glucagon loses the capacity to augment myocardial contractility and activate adenyl cyclase in hearts derived from cats in chronic failure.
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PMID:Effects of experimental heart failure on the capacity of glucagon to augment myocardial contractility and activate adenyl cyclase. 544 51

1. The inotropic activity of glucagon was compared with catecholamines and cardiac glycosides by in vitro procedures which were able to differentiate between the activities of the latter two groups.2. The frequency-force curve for glucagon resembled that of noradrenaline at low stimulation frequencies (1 and 2/min) and that of ouabain at more rapid frequencies of stimulation.3. Noradrenaline and adrenaline increased the amplitude of contraction of cat papillary muscles and markedly shortened the time to reach peak tension. Ouabain and glucagon increased tension without any change in the time to peak tension.4. Noradrenaline caused a rapid onset and rate of rise of contraction of cat aortic strips, whereas the response to ouabain was slow in onset and rate of development. Glucagon had no effect on this preparation, even at high concentrations.5. Manganese ions caused a shift of the dose-response curve to ouabain and glucagon, but not to noradrenaline or calcium. In 0.5 mM Ca media, the response to ouabain was abolished and the curve to noradrenaline shifted.6. When glucagon was added to an atrial preparation, the time to the initial increase in tension and the time to maximal tension was intermediate between that necessary for noradrenaline and that necessary for cardiac glycosides.7. Propranolol blocked the inotropic response to noradrenaline, but not to either ouabain or glucagon.8. A relative measure of contraction-dependency was described. Cardiac glycosides exhibited a greater degree of contraction-dependency than either noradrenaline or glucagon.9. Adrenaline elevated the depressed plateau of the action potential from calf and sheep Purkinje fibres, but ouabain and glucagon were without effect.10. Electrophysiological measurements demonstrated that moderate concentrations of glucagon exerted only a small effect in prolonging atrial and ventricular action potentials.11. Several pharmacological blocking drugs and other inotropic agents did not potentiate or block the inotropic response to glucagon. Reserpine pretreatment increased the response to glucagon.12. It was concluded that glucagon has its own spectrum of inotropic activity and does not completely mimic the effects of either ouabain or noradrenaline.
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PMID:Comparison of the inotropic response to glucagon, ouabain and noradrenaline. 549 91

Norepinephrine is generally regarded as an inhibitor of insulin release. It has been shown, however, that under hyperglycemic circumstances, norepinephrine infused at a high dose may also stimulate insulin secretion. The goals of this study were, under normoglycemic conditions, to confirm this stimulatory effect and to determine whether a beta-adrenergic mechanism or central neural pathways were involved. Secretion of pancreatic somatostatin and glucagon were also studied. Fasted, anesthetized dogs had norepinephrine (2 micrograms X kg-1 X min-1) infused into a peripheral vein for 60 min; blood was sampled from the pancreaticoduodenal vein. Norepinephrine stimulated insulin, somatostatin, and glucagon secretion without significant changes in either blood glucose concentration or pancreaticoduodenal venous blood flow. The stimulatory effect of norepinephrine on the three hormones was abolished by propranolol pretreatment, thus implicating a beta-adrenergic mechanism. Because bilateral cervical vagotomy prevented stimulation of insulin secretion by norepinephrine, central neural pathways must have been involved in the stimulatory process. However, norepinephrine-induced glucagon secretion was not decreased by vagotomy, showing that the stimulation was due to either a direct action on the pancreatic A cell or of a central pathway not mediated via the vagus nerve. Norepinephrine-induced somatostatin secretion was partly reduced by vagotomy, indicating that several mechanisms could be implicated.
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PMID:In vivo stimulation of pancreatic hormone secretion by norepinephrine infusion in the dog. 614 71

Ketogenesis may be controlled at several sites. Lipolysis with release of plasma nonesterified fatty acid (NEFA) substrate is the first step. Plasma NEFA are taken up by the liver in a concentration-dependent fashion and, after conversion to the acyl-CoA derivative, may either be reesterified or enter the mitochondria via the carnitine shuttle. After beta-oxidation the resultant acetyl-CoA may either be converted to ketone bodies that are then released into the circulation or be condensed with oxaloacetate and enter the tricarboxylic acid cycle, the third potential control point. In humans, infusion of epinephrine causes a transient two- to threefold increase in fatty acids, glycerol, and ketone bodies. Insulin levels show a small absolute increase. Norepinephrine has similar effects, although insulin levels tend to be suppressed and glucagon levels rise somewhat. If somatostatin is added simultaneously, the lipolytic and ketogenic effects are accentuated and prolonged. Dopamine, in a high dose, has no effect on ketone bodies alone but shows small increases in NEFA and ketone bodies in the presence of somatostatin and may play a modulatory role in ketogenesis. The ketogenic effect of catecholamines could thus be in the adipocyte or in the liver. Studies with perfused liver or hepatocytes showed only trivial effects on ketogenesis even with supraphysiological doses of catecholamines. Furthermore infusion studies in rats showed decreased rather than increased ketogenesis with no change in NEFA levels. The data suggest that a) there are species differences, and b) in humans epinephrine- and norepinephrine-induced increases in ketogenesis are secondary to increases in NEFA substrate supply.
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PMID:Mechanisms of catecholamine effects on ketogenesis. 614 93

Adult rat parenchymal hepatocytes in primary culture can be induced to enter into DNA synthesis and mitosis. The optimal conditions for hepatocyte replication are low plating density (less than 10,000 cells/sq cm) and 50% serum from two-thirds partially hepatectomized rats (48 hr after hepatectomy). Approximately 80% of the hepatocytes enter the cell cycle, and most of these cells go through mitosis. The replicating hepatocytes remain positive for glucose-6-phosphatase and negative for gamma-glutamyl transpeptidase, and they accumulate fat, in analogy to regenerating liver. Most of the replicating hepatocytes enter into multiple consecutive rounds of DNA synthesis. Dose-response studies between control animal serum and hepatocyte labeling index indicate that in unoperated animals the serum contains substances stimulatory as well as inhibitory for hepatic growth, with the inhibitory effect prevailing at high concentrations. After partial hepatectomy, the inhibitory activity disappears whereas the hepatopoietin activity reaches almost 90% of maximal biological effectiveness at 25% serum concentration. Addition of hormones to the system shows that the hepatopoietin activity is not identical to epidermal growth factor, platelet-derived growth factor, thyroxine, glucagon, or hydrocortisone. Norepinephrine abolishes the difference between control and hepatectomized serum but does not restore hepatopoietin activity when added to heat-inactivated serum. The results show that this system of replicating hepatocytes can be used to investigate the trophic factors that control growth of normal and neoplastic hepatocytes.
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PMID:Liver regeneration studies with rat hepatocytes in primary culture. 621 20

The present experiments tested the ability of putative neurotransmitters and neuromodulators to regulate cyclic adenosine 3':5'-monophosphate (cAMP) levels in rat hippocampal slices. Slices from ovariectomized adult female rats were equilibrated for 1 hr and incubated for 20 min with various test compounds, and cAMP was extracted and quantified using a competitive protein-binding assay. Norepinephrine, adenosine, histamine, and prostaglandins E1 and E2 alpha, induced moderate (1.5- to 5-fold) increases in cellular cAMP, whereas dopamine, serotonin, prostaglandin F2 alpha, and glutamate were relatively ineffective. Most striking was the observation that vasoactive intestinal peptide (VIP) produced marked elevation (approximately 80-fold at 6 microM) of hippocampal slice cAMP content. In contrast, other peptides produced only 2-fold increased (glucagon, somatostatin) or no change in cellular cAMP levels (enkephalins, LHRH, ACTH analogue, arginine vasopressin). Significant elevations in cAMP were seen with VIP concentrations as low as 20 nM; the cAMP response was half-maximal at 1 microM VIP and maximized between 10 and 20 microM. At maximally effective concentrations, VIP was 86% as effective in increasing cAMP as maximal concentrations of forskolin, a compound which activates adenylate cyclase in most cell types. The cAMP response to 10 microM VIP was pronounced after a 1-min incubation (16-fold elevations) and was maximal at 30 min (140-fold elevation). When slices from other brain areas were compared, it was found that regions known to contain high levels of VIP (cerebral cortex) also responded to VIP treatment with 30- to 50-fold elevations in cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Activators of cyclic adenosine 3':5'-monophosphate accumulation in rat hippocampal slices: action of vasoactive intestinal peptide (VIP). 631 11

Effects of noradrenaline on the portal and aortic plasma pancreatic hormone concentrations were studied in the cold- and heat-acclimated rats in order to know possible roles of these hormones in temperature acclimation. Noradrenaline (NA) infusion (2 micrograms/min, i.v., 30 min) effected greater elevation of colonic temperature (Tc) in the cold-acclimated rats (CA) than in the warm controls (WC), and did not influence Tc in the heat-acclimated rats (HA) under hexobarbital anesthesia. Portal and aortic glucagon levels increased in the NA-infused CA and HA, but no changes were observed in the NA-infused WC. NA-infusion did not affect the portal and aortic insulin levels in WC and CA, but increased aortic insulin level in HA. Aortic glycerol and free fatty acid (FFA) levels increased in all NA-infused groups. Portal and jugular vein FFA levels increased in NA-infused WC, but did not in NA-infused CA and HA. Neither NA infusion, nor glucagon was related to the elevation of Tc in HA. These results suggest that temperature acclimation modifies a glucagon-releasing action of NA and the NA-released glucagon could cooperate with NA to enhance nonshivering thermogenesis in the cold.
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PMID:Noradrenaline-induced secretions of pancreatic hormones in cold- and heat-acclimated rats. 636 8

Norepinephrine, dopamine and serotonin directly stimulated glucagon secretion by isolated perifused hamster islet. Propranolol blocked norepinephrine, dopamine and serotonin-stimulated glucagon release, suggesting that norepinephrine, dopamine and serotonin may modulate glucagon secretion via a beta-adrenergic mechanism. Dopamine and serotonin may exert their action directly via the beta receptor, stimulate residual adrenergic nerve terminals, or the release of other islet biogenic amines. We conclude that part of the stimulating effect of norepinephrine on glucagon release is beta adrenergically mediated and that dopamine and serotonin may affect glucagon secretion either directly or through the release of neurotransmitters that lead to glucagon release. Thus the intra-islet released dopamine and serotonin may contribute to the islets paracrine system by stimulating intra-islet adrenergic neurons.
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PMID:Biogenic amine regulation of glucagon secretion. 639 23

Frog liver adenylate cyclase was characterized with respect to divalent cation interaction and hormonally stimulated activities. The enzyme catalyzed the synthesis of cyclic [32P]3',5'-AMP from alpha-32P-labeled ATP. The activity of the enzyme was linear with time and protein concentration. The Km for ATP was 0.5 mM, in the presence or absence of stimulators. The temperature optimum was 25 degrees. GTP (10(-4) M) increased the stimulation of adenylate cyclase by epinephrine. Similar activities were obtained using 5 mM Mg2+ or Mn2+. At higher concentrations, both ions inhibited epinephrine-stimulated, but not basal or fluoride-stimulated activities. Approximately equivalent hormonal stimulation was obtained with maximal stimulating concentrations of epinephrine, isoproterenol, glucagon, and prostaglandin E1. Norepinephrine was less stimulatory. Only catecholamine-stimulated activities were inhibited by propranolol (10(-5) M). The data suggest that catecholamines stimulate frog liver adenylate cyclase through interactions with beta adrenergic receptors. The adenylate cyclase in frog liver differs from its mammalian counterpart in its response to temperature and maximally stimulatory concentrations of hormones.
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PMID:Catecholamine and divalent cation effects on frog liver adenylate cyclase. 660 83

After 30 min infusion of glucagon or noradrenaline, blood flow through brown adipose tissue (BAT) from various sites was investigated with the aid of 113Sn-labeled microspheres under hexobarbital anesthesia in cold-acclimated (CA), heat-acclimated (HA), and warm control (WC) rats. Glucagon increased cardiac output in both CA and HA, while noradrenaline increased it in HA but not in CA. Blood flow through BAT as well as the fractional distribution of cardiac output to BAT increased by glucagon dose-dependently and reached a maximum level in a dose of 2 micrograms/min. These glucagon-induced responses were significantly higher in CA and smaller in HA as compared with WC. Noradrenaline in a dose of 2 microgram/min caused larger responses than glucagon in all groups. Glucagon- or noradrenaline-induced blood flow per unit weight of BAT increased or tended to increase by cold acclimation. These results suggest that an in vivo enhanced glucagon-induced thermogenesis in cold-acclimated BAT is partly due to an increased blood flow through this tissue.
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PMID:Effects of glucagon and noradrenaline on the blood flow through brown adipose tissue in temperature-acclimated rats. 663 71


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