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)

1. The administration of glucagon or N6O2'-dibutyryl cyclic AMP to fed rats by intraperitoneal injection was associated with a 2-fold increase in the amounts of endogenous Pi and ATP, and an increase in the rate and extent of transport of exogenous Pi (measured in either the presence or the absence of Ca2+) in mitochondria subsequently isolated from the liver. No change was observed in either the maximum rate of transport of exogenous Pi or in the rate of 32Pi exchange. 2. The changes induced by glucagon and dibutyryl cyclic AMP were markedly decreased by the co-administration of cycloheximide. 3. The administration of insulin to rats resulted in an increase of about 1.3-fold in the concentration of endogenous mitochondrial Pi 4. The amounts of endogenous Pi in mitochondrial isolated from the livers of starved rats were 3 times those in mitochondria isolated from fed animals. 5. It is concluded that the liver mitochondrial phosphatetransport system may be an important site of hormone action. 6. In the course of these experiments, it was shown that Ca2+ markedly stimulates mitochondrial phosphate transports.
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PMID:Effects of hormones and N6O2'-dibutyryl-adenosine 3' :5'-cyclic monophosphate, administered in vivo, on phosphate transport and metabolism in isolated rat liver mitochondria. 21 Jul 63

1. The administration of glucagon to fed rats by intraperitoneal injection, or the perfusion of livers from fed rats with glucagon by the method of Mortimore [Mortimore (1963) Am.J. Physiol. 204, 699--704] was associated with increases of 15- and 5-fold respectively, in the time for which a given load of exogenous Ca2+ is retained by mitochondria subsequently isolated from the liver. This effect of glucagon was (a) also induced by N6O2'-dibutyryl cyclic AMP, (b) completely blocked by cycloheximide, (c) relatively slow in onset (15--60 min) and (d) associated with a stimulation of about 20% in the rates of ADP-stimulated oxygen utilization and Ca2+ transport measured in the presence of succinate. 2. Perfusion of livers with glucagon resulted in the isolation of mitochandria which showed a 50% increase, no significant change and a 40% increase in the concentrations of endogenous Ca, Mg and Pi respectively, when compared with mitochondria isolated from control perfused livers. 3. The administration of insulin or adrenaline to fed rats induced increases of 10- and 8-fold respectively, in the time for which Ca2+ is retained by isolated liver mitochondria. Perfusion of livers with insulin had no effect on mitochondrial Ca2+ retention time. 4. The perfusion of livers from starved rats with glucagon, or the administration of either glucagon or insulin to starved rats, increased by about 2.5- and 15-fold respectively, the time for which isolated mitochondria retain Ca2+. 5. Mechanisms which may be responsible for the observed alterations in Ca2+-retention time are discussed.
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PMID:Effects of glucagon and N6O2'-dibutyryladenosine 3':5'-cyclic monophosphate on calcium transport in isolated rat liver mitochondria. 21 32

In idiopathic or generalized epilepsy, serum glucose and cholesterol concentrations tend to be low, especially just before the seizure. Glucose tolerance curves are abnormal and variable. The electrolyte balance is disturbed, and epileptics tend to go readily into alkalosis. Serum [Na+] is usually unaffected, but [K+] is normal to low between attacks and increases during and after the seizure. Serum [Cl-] is usually high just before the seizure. Epileptics are generally mildly hypocalcemic, especially in the period before the seizure. Serum urea and nonprotein nitrogen values are low between paroxysms but increase after the seizure. Serum protein concentration is usually normal. Stress, which releases epinephrine and corticotropin, results in high serum citrate concentration, which probably contributes to decreased serum [Ca2+] just before a seizure. In the healthy individual, any increase in serum citrate is accompanied by increasing [Ca2+]. In the rabbit, convulsions can be induced with corticotropin, a result of increased serum citrate concentration coupled with a decrease in [Ca2+]. The net result is severe hypo-ionic-calcemia. A similar phenomenon has been reported in a few humans. Administration of insulin causes serum citrate concentrations to decrease. Apparently, the dynamic system that controls glucose and lipid metabolism, and thus electrolyte balance, through the hormones epinephrine, corticotropin, insulin, glucagon, calcitonin, and parathormone, is abnormal in the epileptic.
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PMID:Clinical biochemistry of epilepsy. I. Nature of the disease and a review of the chemical findings in epilepsy. 22 Nov 36

Angiotensin II, catecholamines, and vasopressin are thought to stimulate hepatic glycogenolysis and gluconeogenesis via a cyclic AMP-independent mechanism that requires calcium ion. The present study explores the possibility that angiotensin II and vasopressin control the activity of regulatory enzymes in carbohydrate metabolism through Ca2+-dependent changes in their state of phosphorylation. Intact hepatocytes labeled with [32P]PO43- were stimulated with angiotensin II, glucagon, or vasopressin and 30 to 33 phosphorylated proteins resolved from the cytoplasmic fraction of the cell by electrophoresis in sodium dodecyl sulfate polyacrylamide slab gels. Treatment of the cells with angiotensin II or vasopressin increased the phosphorylation of 10 to 12 of these cytosolic proteins without causing measurable changes in cyclic AMP-dependent protein kinase activity. Glucagon stimulated the phosphorylation of the same set of 11 to 12 proteins through a marked increase in cyclic AMP-dependent protein kinase activity. The molecular weights of three of the protein bands whose phosphorylation was increased by these hormones correspond to the subunit molecular weights of phosphorylase (Mr = 93,000), glycogen synthase (Mr = 85,000), and pyruvate kinase (Mr = 61,000). Two of these phosphoprotein bands were positively identified as phosphorylase and pyruvate kinase by affinity chromatography and immunoprecipitation, respectively. Incubation of hepatocytes in a Ca2+-free medium completely abolished the effects of angiotensin II and vasopressin on protein phosphorylation but did not alter those of glucagon. Treatment of hepatocytes with angiotensin II, glucagon, or vasopressin stimulated phosphorylase activity by 250 to 260%, inhibited glycogen synthase activity by 50%, and inhibited pyruvate kinase activity by 30 to 35% (peptides) to 70% (glucagon). The effects of angiotensin II and vasopressin on the activity of all three enzymes were completely abolished if the cells were incubated in a Ca2+-free medium while those of glucagon were not altered. The results imply that angiotensin II, catecholamines, and vasopressin control hepatic carbohydrate metabolism through a Ca2+-requiring, cyclic AMP-independent pathway that leads to the phosphorylation of important regulatory enzymes.
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PMID:The role of calcium ion as a mediator of the effects of angiotensin II, catecholamines, and vasopressin on the phosphorylation and activity of enzymes in isolated hepatocytes. 22 57

We have prepared 125I-labeled physalaemin and have examined the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas. Binding of 125I-labeled physalaemin was saturable, temperature-dependent, and reversible and reflected interaction of the labeled peptide with a single class of binding sites on the plasma membrane of pancreatic acinar cells. Each acinar cell possessed approximately 500 binding sites, and binding of the tracer to these sites could be inhibited by physalaemin [concentration for half-maximal effect (Kd), 2 nM], substance P (Kd, 5 nM), or eledoisin (Kd, 300 nM) but not by cholecystokinin, caerulein, bombesin, litorin, gastrin, secretin, vasoactive intestinal peptide, glucagon, somatostatin, neurotensin, bovine pancreatic polypeptide, leucine-enkephalin, methionine-enkephalin, atropine, or carbamylcholine. With physalaemin, substance P, and eledoisin, there was a close correlation between the relative potency for inhibition of binding of labeled physalaemin and that for stimulation of amylase secretion. For a given peptide, however, a 3-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of amylase secretion, calcium outflux, or cyclic GMP accumulation. These results indicate that dispersed acini from guinea pig pancreas possess a single class of receptors that interact with physalaemin, substance P, and eledoisin and that occupation of 45% of these receptors will cause a maximal biological response.
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PMID:Interaction of physalaemin, substance P, and eledoisin with specific membrane receptors on pancreatic acinar cells. 23 Apr 88

On the dog isolated right ventricular muscle, experiments were carried out in order to elucidate the characteristics of the cholinergic antagonism against the positive inotropic action (PIA) induced via different subcellular mechanisms. The relationship between cyclic AMP and cyclic GMP levels, and contractile force during cholinergic antagonism was assessed. Carbachol (10 microM) by itself decreased only slightly the tension developed, but inhibited prominently the PIAs of isoprenaline, histamine, glucagon, theophylline and papaverine. The action of dibutyryl cyclic AMP was inhibited less than PIAs of other agents mentioned above. In contrast, carbachol did not affect the PIAs of calcium and g-strophanthin. The antagonism by carbachol of PIAs of isoprenaline, histamine, glucagon, theophylline and papaverine was accompanied by a reduction of the intracellular cyclic AMP level elevated previously by these agents, and by an elevation of the intracellular cyclic GMP level. A good correlation was found between changes in the tension developed, and cyclic AMP and cyclic GMP levels during the cholinergic antagonism of PIAs induced by these agents in the dog ventricular myocardium.
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PMID:Correlation of cyclic AMP and cyclic GMP levels with changes in contractile force of dog ventricular myocardium during cholinergic antagonism of positive inotropic actions of histamine, glucagon, theophylline and papaverine. 23 99

The major form of the trypsin-like proteinases from the larvae of the webbing clothes moth Tineola bisselliella has been further purified and some of its properties investigated. It differs from bovine trypsin in several respects. It is anionic at neutral pH, is very stable at alkaline pH, has no requirement for calcium ions for this stability and is very sensitive to urea. It resembles vertebrate trypsins in its complete inhibition by diisopropylfluorophosphate, its pH optimum of 8.5 for hydrolysis of benzoyl-arginine p-nitroanilide and its cleavage specificity against glucagon and the beta-chain of S-carboxymethyl insulin.
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PMID:Properties and specificity of the major anionic trypsin-like enzyme in the keratinolytic larvae of the webbing clothes moth. 23 56

Acute glucagon treatment of intact rats has been found to cause a stimulation of hepatic mitochondrial respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with several NAD-linked substrates and succinate were increased significantly after hormonal treatment and isolation of mitochondria. This stimulation cannot be ascribed to a partial uncoupling effect since State 4 respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with either slightly increased or unchanged. Furthermore, rates of uncoupled respiration with these substrates were also stimulated after hormonal treatment. On the other hand, respiratory rates (State 3, 4, and uncoupled) with ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine as substrate were unaffected by glucagon treatment. The hormonally stimulated rates of respiration produced a corresponding increase in the rate of generation of high energy state as indicated in measurements of Ca2+ uptake by isolated mitochondria. Rates of Ca2+ uptake were monitored by two methods: measurement of initial rates of proton ejection following CaCl2 additions and measurement of disappearance of Ca2+ from the suspension medium using murexide as indicator in a dual wavelength spectrophotometer. A significant stimulation in the initial rate of succinate-dependent Ca2+ uptake was noted after glucagon treatment of animals and isolation of hepatic mitochondria. No effect of the hormonal treatment was seen on the extent of Ca2+ uptake or the stoichiometry of H+ ejected per Ca2+ taken up. That the hormonal effect on Ca2+ transport is at the level of the substrate-induced generation of high energy state is indicated by the observation that no effect of glucagon treatment is seen on ATP-dependent Ca2+ uptake. Glucagon-induced changes in the activities of substrate-metabolizing enzymes are considered unlikely for the following reasons: (a) previously published data showed a lack of a hormonal effect on pyruvate-metabolizing enzymes and (b) data in this study showing no effect of glucagon treatment on the activity of NAD-malate dehydrogenase as measured in mitochondrial lysates. All of these observations are consistent with either an activation of mitochondrial substrate transport and/or a stimulation of mitochondrial electron transport by glucagon treatment. Regardless of the exact mechanism involved, the effect of the hormonal treatment is to produce an increase in ATP synthetic and ion-pumping capability during a period of increased energy demand, i.e. increased gluconeogenesis.
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PMID:Glucagon stimulation of mitochondrial respiration. 24 Aug 44

A sensitive RIA for human calcitonin has been developed which can detect 1-2 pg hormone. This procedure permits the measurement of the low concentrations of calcitonin in the unextracted plasma of normal human subjects. In 55 normal adults, mean plasma calcitonin was 24 pg/ml with an SD of +/- 18 pg/ml, an SE of +/- 2 pg/ml, and a range of less than 10 - 75 pg/ml. There were no discernible age or sex differences in basal hormone concentration. Infusions of calcium, pentagastrin, and glucagon stimulated plasma calcitonin, whereas food and oral calcium did not. The stimulatory effect of pentagastrin was greater in males than in females. These data demonstrate that the low concentration of calcitonin in humans can be stimulated by several secretagogues and suggest that females may have decreased calcitonin reserve.
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PMID:Calcitonin secretion in normal human subjects. 26 89

Recent clinical experiences with 34 Z-E patients indicates that the clinical features and course of the syndrome is less dramatic than described originally. Eighty-five per cent of the patients presented stories of abdominal complaints lasting more than five years and resembling the complaints presented by duodenal ulcer patients (DU). Ulcers were present in 91 per cent of the patients. Fifty-one per cent had either ectopic or multiple ulcers. One third had a single duodenal ulcer resembling an ordinary ulcer. No patients died from complications to the ulcer diathesis. Marked hypersecretion of acid and gastrin was present in the ZE group (BAO:33.7 +/- 7.4; PAO:62.8 +/- 6.1 meq H+/h; gastrin: 5094 pmol/l), but because of great individual variation in the ZE, some overlapping with the acid and gastrin measurements of the DU was seen. The diagnostic value of provocative tests using secretin, calcium, glucagon and food stimulations demonstrated a considerable overlapping between the two groups, indicating that these tests are of little clinical value. Tumours were found in half the patients, revealing malignancy in ten. The ZE can be diagnosed in most cases by combining symptomatology, with measurements of acid and gastrin.
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PMID:The clinical diagnosis of the Zollinger-Ellison syndrome. 29 36


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