scholarly journals Epidermal growth factor administration decreases liver glycogen and causes mild hyperglycaemia in mice

1996 ◽  
Vol 315 (1) ◽  
pp. 289-293 ◽  
Author(s):  
Montserrat GRAU ◽  
Francesc TEBAR ◽  
Ignasi RAMÍREZ ◽  
Maria SOLEY
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Rat Hepatocytes ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Isolated Cells ◽  
Experimental Conditions ◽  
Epidermal Growth ◽  
Mouse Hepatocytes

Several laboratories report different effects of epidermal growth factor (EGF) on glycogen metabolism in hepatocytes. The discrepancies may be attributed to differences in the experimental conditions. It is therefore important to establish the actual effect of EGF in vivo. Because large physiological variations of EGF concentration in plasma occur in mice, we used this species to address this question. In freshly isolated mouse hepatocytes, EGF increased glycogen degradation in a dose-dependent manner. The maximal effect (36% increase over basal glycogenolysis) was smaller than maximal effects of classical glycogenolytic hormones like adrenaline or glucagon (more than 150% increase over basal). This is in keeping with the smaller effect of EGF on phosphorylase a activity. In contrast with these hormones, EGF did not inhibit glycolysis. Thus these effects of EGF in mouse hepatocytes are similar to those recently described by us in rat hepatocytes [Quintana, Grau, Moreno, Soler, Ramírez and Soley (1995) Biochem. J. 308, 889–894]. When administered to whole animals, EGF increased phosphorylase a activity, decreased the glycogen content in the liver and caused mild hyperglycaemia. Taking together the results obtained for isolated cells and for whole animals, we suggest that the glucosyl residues released from glycogen are used mostly by the liver rather than released to the circulation. This would be different from the action of the classical glycogenolytic hormones, adrenaline and glucagon.

scholarly journals Five enzymes of the glycolytic pathway serve as substrates for purified epidermal-growth-factor-receptor kinase

1986 ◽  
Vol 239 (3) ◽  
pp. 691-697 ◽  
Author(s):  
N Reiss ◽  
H Kanety ◽  
J Schlessinger
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Glycolytic Pathway ◽  
Dependent Manner ◽  
Receptor Kinase ◽  
Epidermal Growth

Several enzymes of the glycolytic pathway are phosphorylated in vitro and in vivo by retroviral transforming protein kinases. These substrates include the enzymes phosphoglycerate mutase (PGM), enolase and lactate dehydrogenase (LDH). Here we show that purified EGF (epidermal growth factor)-receptor kinase phosphorylates the enzymes PGM and enolase and also the key regulatory enzymes of the glycolytic pathway, phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in an EGF-dependent manner. Stoichiometry of phosphate incorporation into GAPDH (calculated from native Mr) is the highest, reaching approximately 1. LDH and other enzymes of the glycolytic pathway are not phosphorylated by the purified EGF-receptor kinase. These enzymes are phosphorylated under native conditions, and the Km values of EGF-receptor kinase for their phosphorylation are close to the physiological concentrations of these enzymes in the cell. EGF stimulates the reaction by 2-5-fold by increasing the Vmax. without affecting the Km of this process. Phosphorylation is rapid at 22 degrees C and at higher temperatures. However, unlike the self-phosphorylation of EGF-receptor, which occurs at 4 degrees C, the glycolytic enzymes are poorly phosphorylated at this temperature. Some enzymes, in particular enolase, increase the receptor Km for ATP in the autophosphorylation process and thus may act as competitive inhibitors of EGF-receptor self-phosphorylation. On the basis of the Km values of EGF receptor for the substrate enzymes and for ATP in the phosphorylation reaction, these enzymes may also be substrates in vivo for the EGF-receptor kinase.

Epidermal growth factor stimulates the prolactin synthesis and secretion in rat pituitary cells in culture (GH4C1 cells) by increasing the intracellular concentration of free calcium

1993 ◽  
Vol 128 (4) ◽  
pp. 361-366 ◽  
Author(s):  
Marie Aanestad ◽  
J Sigurd Røtnes ◽  
Peter A Torjesen ◽  
Egil Haug ◽  
Olav Sand ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Intracellular Concentration ◽  
Free Calcium ◽  
Pituitary Cells ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Epidermal Growth

Epidermal growth factor (EGF) stimulated the prolactin (PRL) synthesis and release from the GH4C1 cells in a dose-dependent manner. The ED50 was between 10−11 and 10−10 mol/l. The maximal effect was obtained at 10−9 mol/l EGF for the release, and 10−8 mol/l EGF for the synthesis. EGF stimulated the release of PRL from cell perfusion columns after a lag period of about 30 s. The maximal secretion of PRL occurred about 60 s after the start of stimulation. The PRL secretion declined to basal levels within 2 min. The EGF-stimulated PRL release was additive to the secretion evoked by thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). An instantaneous increase in the intracellular concentration of free calcium, [Ca2+]i, of the GH4C1 cells was observed after the administration of EGF. EGF modified neither the basal nor the TRH-stimulated inositoltrisphosphate production in the GH4C1 cells, and EGF did not show any effect on the cyclic adenosine monophosphate production of these cells.

Quantitative aspects of the effects of insulin, epidermal growth factor and dexamethasone on DNA synthesis in cultured adult rat hepatocytes

1985 ◽  
Vol 109 (3) ◽  
pp. 369-377 ◽  
Author(s):  
Tor-Erik Sand ◽  
Gunnar Brønstad ◽  
Vemund Digernes ◽  
Anne Killi ◽  
Wasfiyeh Amara ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Time Course ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Maximal Effect ◽  
Adult Rat ◽  
Adult Rat Hepatocytes ◽  
Epidermal Growth

Abstract. Epidermal growth factor (EGF) and insulin in combination have previously been shown to initiate S-phase in primary cultures of adult rat hepatocytes. We here describe the detailed time course and dosedependency of the effects of EGF and insulin on DNA synthesis in cultured hepatocytes. The DNA synthesis was assessed either biochemically or autoradiographically with a fairly good correlation between the two methods. DNA synthesis started 24–30 h after plating of the cells and peaked at approximately 70 h. Up to 70% of the cells entered DNA synthesis during this period. EGF and insulin acted synergistically on the DNA synthesis. Dexamethasone raised the DNA synthesis slightly, maximal effect occurred at concentrations above 2.5 nm and this agent was routinely used in the experiments with EGF and insulin. In the presence of 0.4 μm insulin from the time of plating, EGF dose-dependently increased the DNA synthesis with maximal effect at 5–15 nm. When added in combination with 1.7 nm EGF, insulin enhanced the DNA synthesis over the concentration range from 0.1 to 3 nm. These studies show that primary cultures of hepatocytes are useful in assessing the quantitative aspects of the interactions between the growth stimulating effects of hormones.

scholarly journals Epidermal growth factor controls smooth muscle alpha-isoactin expression in BC3H1 cells.

1988 ◽  
Vol 106 (3) ◽  
pp. 797-803 ◽  
Author(s):  
Y C Wang ◽  
P A Rubenstein
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Northern Analysis ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Differentiated Cells ◽  
Epidermal Growth ◽  
Dose Dependent

We have examined the effects of epidermal growth factor (EGF), platelet-derived growth factor, and insulin on the differentiation of a mouse vascular smooth muscle-like cell line, the BC3H1 cells. On the basis of cell morphology and smooth muscle alpha-isoactin synthesis, we demonstrate that EGF at physiological concentrations prevents the differentiation of these cells, whereas platelet-derived growth factor has no apparent effect. The induction of alpha-isoactin synthesis by serum deprivation is inhibited by EGF in a dose-dependent manner with a half-maximal effect at 3-5 ng/ml and a maximal inhibition at approximately 30 ng/ml. Northern analysis also shows that EGF blocks the accumulation of alpha-isoactin mRNA normally observed during cell differentiation. Addition of EGF to differentiated cells results in a repression of alpha-isoactin synthesis, a stimulation of beta- and gamma-isoactin synthesis, and the stabilization of the nonmuscle isoactins. The synthesis of creatine phosphokinase, a muscle-specific noncontractile protein, is also regulated by EGF in a similar fashion. Modulation by EGF of alpha-isoactin expression is not affected by aphidicolin and is therefore independent of its mitogenic effect on these cells. Insulin is not required for observation of the EGF-dependent effects but instead seems to promote differentiation. Our results show that EGF can replace serum in controlling the differentiation of BC3H1 cells.

Comparison of the Mitogenic Activity of Human Epidermal Growth Factor 1-53 and Epidermal Growth Factor 1-48 in Vitro and in Vivo

1996 ◽  
Vol 91 (4) ◽  
pp. 503-507 ◽  
Author(s):  
R. A. Goodlad ◽  
R. Boulton ◽  
R. J. Playford
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Rat Hepatocytes ◽  
In Vivo Studies ◽  
Thymidine Uptake ◽  
Amino Acid Peptide ◽  
Epidermal Growth ◽  
Small And Large Intestine

1. Epidermal growth factor is secreted into the gut lumen as a 53 amino acid peptide in vivo. Several preliminary studies have examined the clinical benefit of recombinant epidermal growth factor in intestinal disease, but there is inconsistency in the form of epidermal growth factor used (some using epidermal growth factor 1–48 and some epidermal growth factor 1–53), making comparisons difficult to evaluate. 2. We therefore examined the relative potency of recombinant epidermal growth factor 1–48 and epidermal growth factor 1–53 in stimulating [3H]thymidine uptake into primary rat hepatocytes at various doses in vitro and on various parameters of proliferation within the gastrointestinal tract when infused intravenously at 50 nmol day−1 kg−1 into rats receiving total parenteral nutrition. 3. Epidermal growth factor 1–53 was about twice as potent as epidermal growth factor 1–48 in its ability to stimulate [3H]thymidine incorporation into rat hepatocytes in vitro. In vivo studies supported this finding as, in both the small and large intestine, epidermal growth factor 1–53 caused about a 30% greater stimulation of intestinal growth than epidermal growth factor 1–48 (P < 0.001). 4. The 1–48 truncated form of epidermal growth factor is less active than the full-length molecule in vitro and in vivo. This must be borne in mind when comparing clinical trials that use different forms of recombinant epidermal growth factor.

scholarly journals Epidermal growth factor receptor kinase translocation and activation in vivo.

1986 ◽  
Vol 261 (18) ◽  
pp. 8473-8480
Author(s):  
D G Kay ◽  
W H Lai ◽  
M Uchihashi ◽  
M N Khan ◽  
B I Posner ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Kinase ◽  
Epidermal Growth
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