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)

Insulin stimulates phosphorylation of both alpha- and beta- subunits of its own receptor in a cell-free system. A solubilized lectin-purified preparation of insulin receptors from rat liver membranes was preincubated with or without insulin at 4 degrees C and labeled for 10 min with Mn[gamma- 32P]ATP; the receptor subunits were isolated by specific immunoprecipitation with anti-receptor antibodies, followed by gel electrophoresis in sodium dodecyl sulfate. In gels run under reduced conditions, two bands (Mr = 135,000 and 95,000) were selectively labeled. These correspond exactly to the position of the alpha- and beta-subunits of the insulin receptor. Labeling of the Mr = 95,000 band was approximately 5-fold that of the Mr = 135,000 band. No labeled bands were detected when identical samples were immunoprecipitated in control serum. Phosphorylation of the receptor subunits required the presence of the divalent cation Mn2+ or Co2+; other cations such as Mg2+, Cr3+, Ca2+, and Zn2+ were ineffective. [gamma- 32P]ATP served as the 32P donor, whereas [gamma- 32P]GTP was ineffective. Phosphorylation of both subunits was stimulated 4-6-fold after a 60-min exposure to 10(-7) M pork insulin. Insulin-stimulated phosphorylation was half-maximal after 5 min of incubation with 10(-7) M insulin or after 18 h with 3 X 10(-10) M hormone. The enhanced phosphorylation was specific for insulin and its analogs; guinea pig insulin was about 2% as potent as pork insulin, whereas epidermal growth factor, adrenocorticotropic hormone, and glucagon, as well as cAMP, were ineffective. The rapidity and specificity of this reaction, as well as the presence of all necessary components in the plasma membrane, suggest that insulin-mediated receptor phosphorylation is one of the earliest biochemical steps following insulin binding.
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PMID:Characterization of insulin-mediated phosphorylation of the insulin receptor in a cell-free system. 633 57

A low concentration (10(-11) mol/l) of epidermal growth factor (EGF) and/or an equimolar (10(-14) mol/l) mixture of glucagon and insulin stimulated DNA synthesis in hepatocytes in 4-day-old primary cultures of neonatal rat liver. EGF seems to have acted by inducing quiescent hepatocytes to begin cycling, while the glucagon-insulin combination seems to have acted mainly by shortening the cell cycle time. Incubation in low calcium medium blocked untreated hepatocytes in the G1 phase of their cycle and prevented EGF and the glucagon-insulin mixture from stimulating DNA synthesis. Nevertheless, hepatocytes in calcium-deficient medium did respond to these agents, as they reached a late stage of prereplicative development before being blocked: in fact, they initiated DNA synthesis soon after the addition of calcium. EGF, but not the glucagon-insulin combination, also enabled the already cycling hepatocytes (but not the newly activated ones) to overcome the block imposed by the extracellular calcium deficiency after a delay of several hours.
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PMID:The calcium-dependence of the stimulation of neonatal rat hepatocyte DNA synthesis and division by epidermal growth factor, glucagon and insulin. 634 38

In primary cultured hepatocytes of adult rats epidermal growth factor (EGF) caused 2- to 3-fold induction of glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6P dehydrogenase) within 2 days. The effect of EGF was additive with a similar effect of insulin. The half-maximum dose of EGF for the induction was 1 ng/ml. Induction of this enzyme by these hormones was shown by immunotitration to be due to increase of the amount of enzyme. Furthermore, this increase in the amount of enzyme was found to result from increase of syntheses of mRNA and enzyme protein. In contrast, the induction of malic enzyme (EC 1.1.1.40, L-malate:NADP+) oxidoreductase) by insulin plus triiodothyronine was strongly suppressed by the concomitant addition of EGF. Induction of G6P dehydrogenase by EGF, like that by insulin, was not suppressed by either glucagon or dibutyryl cAMP, whereas that of malic enzyme was suppressed additively by EGF and dibutyryl cAMP. EGF also suppressed stimulation of lipogenesis by insulin, measured as incorporation of [1-14C]acetate into triglycerides and phospholipids. Another difference between the inductions of G6P dehydrogenase and malic enzyme was in their dependence on cell density; G6P dehydrogenase induction by insulin and EGF was high at low cell density (3 X 10(4) cells/cm2) and less at higher cell density (13 X 10(4) cells/cm2), whereas induction of malic enzyme was high at higher cell density and less at lower cell density. These results are consistent with the dual role of G6P dehydrogenase in lipogenesis in resting cells and in synthesis of nucleic acid in growing cells. Malic enzyme plays a role only for lipogenesis in mature hepatocytes.
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PMID:Reciprocal effects of epidermal growth factor on key lipogenic enzymes in primary cultures of adult rat hepatocytes. Induction of glucose-6-phosphate dehydrogenase and suppression of malic enzyme and lipogenesis. 635 85

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.
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PMID:Colloidal gold: a pluripotent receptor probe. 635 33

Hepatic stimulator substance (HSS), a partially purified extract of weanling or regenerating adult rat liver, is an organ-specific stimulator of liver growth in vivo and in vitro. The HTC hepatoma cell line is particularly responsive to HSS. The present experiments show that HSS will stimulate HTC cells in the complete absence of serum, although graded doses of fetal cal serum (FCS), from 0.1 to 5.0%, will increase the degree of stimulation in a dose-dependent manner. In contrast, when HSS is absent, increasing doses of FCS above 0.5% inhibit DNA synthesis. Much of this inhibition is removed by prior dialysis of the FCS and maximum enhancement of the HSS-induced stimulation occurs with only 0.1-0.5% of the dialysed FCS. Sera from older animals have less or even negative effect. Evidence is presented to show that the enhanced stimulation by HSS in the presence of serum is not due to insulin, glucagon, epidermal growth factor (EGF), or platelet derived growth factor (PDGF) and that HSS does not act via a shared receptor for one of these hormones. These experiments provide further evidence that HSS is a unique stimulator of liver growth and lend support to a model of organ-specific growth control.
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PMID:Stimulation of HTC hepatoma cell growth in vitro by hepatic stimulator substance (HSS). Interactions with serum, insulin, glucagon, epidermal growth factor and platelet derived growth factor. 636 7

The frontal ganglion of the adult forms of the tobacco hornworm, Manduca sexta, was investigated immunocytochemically for the occurrence of the gastro-entero-pancreatic (GEP) neurohormonal peptides, namely insulin, nerve growth factor, epidermal growth factor, insulin C-peptide, somatostatin, glucagon, glicentin, pancreatic polypeptide (PP), polypeptide YY (PYY), secretin, vasoactive intestinal peptide (VIP), gastric inhibitory peptide (GIP), gastrin, cholecystokinin (CCK), enkephalin, alpha- and beta-endorphins, substance P, neurotensin, bombesin, motilin, ACTH, serotonin, and calcitonin. Among all the antisera tested, positive immunostaining was obtained with anti-insulin B-chain serum only. The insulin B-chain immunoreactivity was localized in 4-6 large (30-40 microns) neurons, in the neuropile, and in the recurrent nerve. It is speculated that the insulin-like immunoreactive material may be transported to the neurohaemal organ (corpora cardiaca) through the nervi cardiaco-somatogastrici.
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PMID:Immunocytochemical evidence for the occurrence of insulin in the frontal ganglion of a Lepidopteran insect, the tobacco hornworm moth, Manduca sexta L. 637 93

The influence of epidermal growth factor (EGF), 0.75 micrograms g1; insulin, 1.5 micrograms g-1; glucagon, 1.25 micrograms g-1 and their combinations on the activities of hepatic pyruvate kinase (PK) and malic enzymes (ME) was monitored. Male CD2F1 mice were treated toward the end of the light or dark periods, 9 or 23 hours after lights on (9 or 23 HALO), and subgroups of six mice were killed at 4, 8 or 12 hr post-treatment. PK and ME activities from control mice were well characterized by cosine curves. The PK activity was maximal when ME activity was minimal at the transition from light to dark (9 HALO plus 4 hr) and PK was at a minimum when ME was highest (23 HALO plus 4 hr). Both enzymes were influenced by at least one peptide hormone, and the effects were strongly circadian-stage dependent. The only effect attributed to EGF was an increase of PK activity (23%) 12 hr after injection at 23 HALO. PK activity was increased by insulin (23%) at 23 HALO (4 hr after injection), but not at 9 HALO, and decreased (17%) by glucagon 12 hr after injection at 9 HALO. Several reductions in PK activity in response to various combinations of peptides were observed, and appeared to be caused by glucagon but influenced by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circadian dependent effect of epidermal growth factor, insulin and glucagon on hepatic pyruvate kinase and malic enzyme of mice. 640 Jun 62

The culture conditions found to result in stable proliferation of normal rat hepatocytes are: (i) subconfluent cell densities; (ii) serum-free medium; (iii) hormonally defined medium containing epidermal growth factor, insulin, glucagon, prolactin, and other growth factors; and (iv) substrata of liver extracellular matrix depleted of growth inhibitors. Serum was found deleterious to parenchymal cells: it was inhibitory to the expression of liver-specific functions, cytostatic to parenchymal cells at all seeding densities, and cytotoxic to them at low seeding densities. These studies emphasize the relevance of synergies in the influences of hormones and extracellular matrix in regulating hepatocellular physiology.
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PMID:Hepatocyte proliferation in vitro: its dependence on the use of serum-free hormonally defined medium and substrata of extracellular matrix. 658 89

A single exposure to a low concentration (10(-9) mole/l) of exogenous arachidonic acid or of prostaglandins of A, E, and F series significantly stimulated primary neonatal rat hepatocytes to enter S phase irrespective of whether the extracellular calcium concentration was high (i.e., 1.8 mmole/l) or markedly reduced (i.e., 0.01 mmole/l). Similarly, a single treatment with an even smaller (10(-10) mole/l) dose of the known tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA), phenobarbital, and nafenopin enhanced hepatocytic DNA synthesis when the environmental calcium level was both high and low. By contrast, a single application of a small concentration (10(-11)-10(-10) mole/l) of hormones such as epidermal growth factor (EGF), glucagon, and insulin, and of drugs such as imidazole and indomethacin only increased the hepatocytic flow into DNA synthesis when the extracellular calcium was high. These findings reveal that the mechanisms of physiological or pharmacological, calcium-dependent stimulation of hepatocellular growth are likely to be different from those of pathological, calcium-independent stimulation, as the latter, but not the former, would involve prostaglandin-mediated metabolic processes.
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PMID:The tumor promoters TPA, phenobarbital, and nafenopin and the prostaglandins of A, E, and F series overcome the G1/S block imposed by extracellular calcium deprivation on neonatal rat hepatocytes. 658 44

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)
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PMID:Cholesterol synthesis by human fetal hepatocytes: effects of hormones. 672 9


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