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)

During treatment of primary cultured hepatocytes with either glucagon or isoproterenol for several hours, the stimulations of cAMP formation by these hormones decreased time dependently. Glucagon treatment also reduced the response to isoproterenol, but isoproterenol treatment did not decrease the response to glucagon. Treatment with isoproterenol caused more rapid desensitization than treatment with glucagon. Assays of glucagon and beta-adrenergic receptors showed that the receptor number of only the hormone with which the cells were treated decreased and that dissociation constants of the receptors did not change. Moreover, in glucagon-desensitized cells, the effect of GTP on competition of the bindings of antagonist and agonist for the beta-adrenergic receptor did not change. After treatment with isoproterenol, stimulation of adenylate cyclase activity by the agonist was decreased without any decrease in the stimulations of activity by other effectors. In contrast, glucagon treatment greatly decreased the stimulations of activity by glucagon, isoproterenol, and guanyl-5'-yl imidodiphosphate and slightly decreased that by fluoride. However, after glucagon treatment, the cells showed normal responses to cholera toxin of activation of adenylate cyclase and ADP-ribosylation of guanine nucleotide binding regulatory protein (Ns). The maximal response of glucagon-treated cells to forskolin was about two-thirds that of untreated cells and this treatment also impaired the shift toward a low Kact value for forskolin observed in the presence of either glucagon or isoproterenol. These results indicate that isoproterenol caused homologous desensitization consisting of only a "down regulation" of the beta-adrenergic receptor, whereas glucagon caused heterologous desensitization, mainly by alteration of the Ns component, as well as "down regulation" of glucagon receptor. This altered Ns seems to be coupled normally to the beta-adrenergic receptor, but to have impaired coupling to the catalytic component of adenylate cyclase.
 ...
PMID:Mechanism of heterologous desensitization of the adenylate cyclase system by glucagon in primary cultures of adult rat hepatocytes. 633 78

To gain insight into the mechanisms responsible for the impaired glycogenolytic response to glucagon and the diminished ketogenic capacity of newborn guinea pig, we studied the ontogeny of insulin and glucagon receptors, and the responsiveness of the adenylate cyclase complex to glucagon, PGE1, NaF, and cholera toxin in liver plasma membrane from fetal (58 d, late gestation, and 65 d, term) and adult guinea pigs. The number of insulin receptors (x 10(-10) M/L) was least in 58-d fetus (3.0 +/- 0.4; mean +/- SEM) and increased 3-fold in 65 d fetus (8.8 +/- 0.6; P less than 0.01). In adult guinea pig, both insulin receptor number (6.0 +/- 0.7) and average affinity constant (1.20 +/- 0.08 x 10(8) M-1) were significantly lower (P less than 0.01) compared with 65-d fetus. The number of glucagon receptors remained unchanged between 58-d and 65-d fetuses, but both average and high affinity association constants were significantly higher at d 65. In contrast to the lower capacity and affinity of insulin receptors in the adult compared with term fetus, the total glucagon receptor number (x 10(-10) M/L) in adults (7.2 +/- 0.8) was twice that of the 58 d (3.2 +/- 0.2) and 65 d (3.2 +/- 1.0) fetuses. The average affinity constant (x 10(8) M-1) in adult (3.8 +/- 0.2) was, however, significantly lower than the two fetal groups (58 d, 5.0 +/- 0.3; P less than 0.05 and 65 d, 8.1 +/- 1.0; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Ontogeny of insulin and glucagon receptors and the adenylate cyclase system in guinea pig liver. 633 Jun 58

Colloidal gold is an electron-dense, lyophobic colloid that readily forms a stable electrostatic interaction with a variety of macromolecules. Monodispersed colloids ranging from 3-150 nm in diameter can be produced to provide the researcher with flexibility in selecting the optimally sized probe. Gold labeling of antibodies and lectins has been extensively used to study surface antigens and cell components. Recently, the use of gold labeling has been extended to study receptor-ligand binding, enzyme-substrate reactions, and transcellular pathways. Published applications include gold labeling of metabolites (low-density lipoproteins), enzymes (DNAase and RNAase, RNA polymerase, thrombin, collagenase, elastase), hormones (insulin, epidermal growth factor, glucagon), circulating plasma proteins (asialoglycoprotein, alpha 2-macroglobulin, factor VIII-von Willebrand factor), and endotoxins (tetanus toxin, cholera toxin). This broad spectrum of applications emphasizes the versatility and usefulness of colloidal gold as a probe in areas of cell biology related to receptors, endocytosis, transport, and functions of proteins.
 ...
PMID:Colloidal gold: a pluripotent receptor probe. 635 33

The gastrointestinal hormones, which are continuously increasing in number, have certain effects which could play a part in the pathogenesis of infectious diarrhoea. This refers especially to VIP, motilin, and enteroglucagon, the plasma concentrations of which are elevated in acute infectious diarrhoea, cholera, and tropical malabsorption. They may act by stimulating intestinal secretion, inhibiting absorption, and altering intestinal motility. In addition, there are some hormonal effects such as those caused by glucagon on motility, by enkephalins on secretion, and by somatostatin on both, which have a therapeutic potential and deserve further investigation.
 ...
PMID:Infectious diarrhoea and gastrointestinal hormones: potential therapeutic implications. 635 26

In previous investigations, we found high rates of cholesterol synthesis in human fetal liver tissue, second only to rates in fetal adrenal tissue. Previous estimates of the amount of cholesterol in the fetus derived from the maternal compartment are in the range of 20%. Thus, the liver may be the principal source of circulating lipoproteins in the human fetus, as is true in the human adult. Low density lipoprotein is the major source of cholesterol used for fetal adrenal steroidogenesis; therefore, it follows that factors regulating cholesterol synthesis in the human fetal liver may indirectly control the rate of steroid secretion by the adrenal cortex. The purpose of the present investigation was to determine if hormones, particularly those produced by the fetal-placental unit, might serve to stimulate cholesterol synthesis in the human fetal liver. The rate of cholesterol biosynthesis was determined by measuring the rate of incorporation of [3H]water into [3H]cholesterol in hepatocytes maintained in culture or by determination of the specific activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in microsomal preparations from human fetal liver. The addition of dexamethasone (10(-10) - 10(-6)M) stimulated cholesterol synthesis up to 2- to 4-fold between days 2 and 6 of exposure. When human fetal liver cells were maintained in the presence of dexamethasone (10(-7)M), the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in microsomal fractions was stimulated 4-fold compared to that in control cells. Cortisol also stimulated cholesterol biosynthesis in a concentration-dependent manner. The addition of 17 beta-estradiol (E2) to the culture medium resulted in stimulation of cholesterol biosynthesis in a concentration-dependent manner from 10(-10) - 10(-7)M. The rate of cholesterol synthesis when E2 was present (10(-7)M) was 4-fold greater than that in untreated cells. Stimulation of cholesterol synthesis by E2 was maintained between 2-7 days of incubation with E2. Estrone, estriol, and E2 (10(-6)M) caused similar increases (3- to 4-fold) in the rates of cholesterol synthesis in human fetal hepatocytes. Finally, progesterone in concentrations greater than 10(-6) M significantly stimulated cholesterol synthesis in human fetal liver cells. In contrast, other hormones and factors, including insulin, glucagon, PRL, GH, dehydroepiandrosterone and its sulfate, epidermal growth factor, fibroblast growth factor, T3, (Bu)2cAMP, and cholera toxin, had no effect on the rate of cholesterol synthesis in human fetal liver cells.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Cholesterol synthesis by human fetal hepatocytes: effects of hormones. 672 9

Adenylate cyclase of the membrane-rich fraction of 24-h cultured islets was inhibited by epinephrine via alpha-adrenergic receptors. Epinephrine was inhibitory only when the enzyme was activated by GTP; the degree of inhibition was highly proportional to the degree of GTP activation. Adenylate cyclase of islets cultured with islet-activating protein (IAP), one of the pertussis toxins, was less susceptible to epinephrine inhibition. The degree of the inhibition was markedly reduced without changes in potency of the catecholamine and in GTP dependence after IAP treatment. None of the other kinetic properties of the enzyme including the affinity for substrate, sensitivity to guanine nucleotide and fluoride activation, and cholera toxin-induced modification of enzymic activity were affected by treatment of islets with IAP, suggesting that neither the catalytic nor the GTP-regulatory component of the membrane adenylate cyclase complex is the site of IAP action. Slight activation of the enzyme by glucagon or adenosine tended to be enhanced by IAP treatment. Thus, a mechanism whereby membrane receptors are linked to adenylate cyclase appears to be modified by exposure of islet cells to IAP.
 ...
PMID:Islet-activating protein. A modifier of receptor-mediated regulation of rat islet adenylate cyclase. 702 47

The removal of extracellular, endogenously produced adenosine in isolated rat adipocytes by treatment with adenosine deaminase enhanced their responsiveness to various lipolytic agents, i.e. the response to catecholamines, glucagon, LH, TSH, and cholera toxin was elicited at concentrations that were 10-500 times lower than those required for the stimulation of lipolysis in untreated cells in vitro. The removal of adenosine from intact fat cells largely potentiated the isoproterenol-stimulated increase in cAmP level. However, a similar treatment of undissociated segments of adipose tissue failed to influence further the response to isoproterenol. These results strongly suggest that in the intact adipose tissue, adenosine and related nucleosides are absent and do not function as modulators of adenylate cyclase or lipolysis. Under these circumstances the estimated "low" physiological concentrations of the neurotransmitters in the adipose tissue are able to modulate lipid mobilization. Previous studies have shown that insulin failed to inhibit lipolysis, induced by micromolar norepinephrine concentrations, in adenosine-free adipocytes. The present study demonstrates that at physiological catecholamine concentrations, insulin is a potent antilipolytic agent.
 ...
PMID:Evaluation of adenosine or related nucleosides as physiological regulators of lipolysis in adipose tissue. 704 12

The effects of net volume secretion on blood flow, oxygen extraction, and oxygen extraction, and oxygen uptake were analyzed in autoperfused segments of cat ileum. Intestinal secretion was induced by local intraarterial infusion of glucagon, histamine, theophylline, prostaglandin E1, or vasoactive intestinal peptide, and, by intraluminal placement of cholera toxin or ricinoleic acid. Net volume secretion rates were determined using a volume recovery method. Intestinal oxygen uptake was increased by all secretagogues. The increases oxygen uptake by the screening intestine resulted from an increased blood flow or oxygen extraction or both. Significant positive correlations between intestinal oxygen uptake and secretion rate were acquired only during cholera toxin, theophylline, and prostaglandin E1, secretion. The results indicate that the metabolic work incurred in the small bowel during secretory states greatly exceeds that reported for the absorptive state.
 ...
PMID:Relationship between intestinal volume secretion and oxygen uptake. 720 2

Molybdate activation of rat liver plasma membrane adenylate cyclase has been examined and compared with the effect of glucagon, Gpp(NH)p and fluoride. Glucagon does not stimulate the detergent solubilized enzyme though molybdate, fluoride, and Gpp(NH)p are effective in this regard. The stimulatory effects of either fluoride or molybdate are additive with those of GTP and do not require guanyl nucleotide to evoke their activation. Neither fluoride nor molybdate can substitute for GTP when glucagon is the activator of rat liver adenyl cyclase. The stimulatory effects of either ion on adenylate cyclase are additive with that produced by glucagon. Activation of adenylate cyclase by either molybdate or fluoride occurs by a mechanism distinct from that of glucagon or guanyl nucleotide. The data presented her suggest that fluoride and molybdate may act via in a similar mechanism of action. Neither ion displays a lag in activation of adenylate cyclase. The pH profiles of fluoride and molybdate-stimulated adenylate cyclase activity are similar, and distinct from guanyl nucleotide-stimulated activity. Cholera toxin treatment of adenylate cyclase blocks fluoride and molybdate stimulation of the enzyme to the same extent, while enhancing the activation obtained with GTP and hormones.
 ...
PMID:Mechanism of molybdate activation of adenylate cyclase. 731 47

The G-protein-mediated coupling of a glucagon receptor to ATP-dependent K channels--KATP--has been studied in insulin-secreting cells using the patch clamp technique. In excised outside-out patches, KATP channel activity was inhibited by low concentrations of glucagon (IC50 = 2.4 nM); the inhibitory effect vanished at concentrations greater than 50 nM. In cell-attached patches, inhibition by bath-applied glucagon was seen most often, although stimulation was observed in a few cases. A dual action of the hormone is proposed to resolve these apparently divergent results. In excised inside-out patches, KATP channel activity was inhibited by addition of beta gamma subunits purified from either erythrocyte or retina (IC50 = 50 pM and 1 nM, respectively). Subsequent exposure of the patch to alpha i or alpha o reversed this effect. In excised inside-out patches, increasing Mg2+ in the bath stimulated the channel activity between 0 and 0.5 nM, but blocked it at higher concentrations (IC50 = 2.55 mM). In most cases (70%), GTP had a stimulatory effect at concentrations up to 100 microns. However, in three cases, similar GTP levels had clear inhibitory effects. In excised inside-out patches, cholera toxin (CTX) caused channel inhibition. Although the effect could not be reversed by removal of the toxin, the activity was restored by subsequent addition of purified alpha i or alpha o. These results are compatible with a model whereby channel inhibition by activated Gs-coupled receptors occurs, at least in part, via association of the beta gamma subunits of Gs with alpha i/alpha o subunits and deactivation of the alpha i/alpha o-dependent stimulatory pathway. On the basis of this hypothesis, a model is developed to describe the effects of G proteins on the KATP channel, as well as to account for the concentration-dependent stimulation and inhibition of KATP channel by Mg2+. An interpretation of the ability of glucagon to potentiate, but not initiate, insulin release is also given in terms of this model and the effects of ATP on KATP channels.
 ...
PMID:Characterization of the G protein coupling of a glucagon receptor to the KATP channel in insulin-secreting cells. 770 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>