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)

The inner medullary collecting duct (IMCD) of the rat consists of two structurally and functionally distinct segments, i.e., the initial and the terminal IMCD. To identify factors that may regulate the transport function in the IMCD segments, we assessed whether catecholamines, carbachol, prostaglandin E2 (PGE2), bradykinin, glucagon, calcitonin, parathyroid hormone, or epidermal growth factor affects adenosine 3',5'-cyclic monophosphate (cAMP) production in microdissected tubules in the presence and absence of arginine vasopressin (AVP, 0.1 nM). All experiments were performed in the presence of 3-isobutyl-1-methylxanthine, and cAMP was measured by radioimmunoassay. Epinephrine (greater than or equal to 50 nM) and clonidine (greater than or equal to 1 microM) markedly decreased AVP-induced cAMP levels in both IMCD segments. However, phenylephrine did not show an effect. The inhibitory effect of epinephrine was blocked by yohimbine (50 nM) but not by prazosin (50 nM). In isolated perfused terminal IMCDs, epinephrine inhibited AVP-stimulated urea permeability. Isoproterenol (1 microM), in the absence of AVP, caused a significant increase in cAMP level only in the initial IMCD. Propranolol (1 microM) inhibited this isoproterenol effect, but atenolol did not. Dopamine (less than or equal to 1 microM) had no effect on cAMP levels in either IMCD segment. Carbachol, PGE2, and the various peptide hormones had no effect on cAMP levels (+/- AVP) in either IMCD segment. We conclude that an adrenergic beta 2-receptor is present only in the initial IMCD, where its occupation increases cAMP production. We conclude also that an adrenergic alpha 2-receptor is present in both IMCD segments, where its occupation inhibits AVP-induced cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormone and autacoid regulation of cAMP production in rat IMCD subsegments. 135 41

This study evaluated the role of insulin, glucagon and the epidermal growth factor (EGF) on liver regeneration after partial hepatectomy. Male Wistar rats, weighing approximately 200 g, were used. A partial hepatectomy, with resection of the medial and left lateral lobes (67.31%), was performed on the control group and seven hormone-treated groups: insulin, glucagon, EGF, insulin plus glucagon, insulin plus EGF, glucagon plus EGF, and a combination of the three hormones. The hormones were administered subcutaneously two days prior to the partial hepatectomy. The groups administered insulin were allowed to drink 20% glucose in water. Another group of rats received simulated operations, i.e., only a laparotomy was performed. The rats were killed at six, 24, 48 and 72 hours after the operation. Remnant liver weight, deoxyribonucleic acid (DNA) content, rate of DNA synthesis, mitotic index, blood glucose and serum insulin levels were measured. The results showed that: 1) the effects of single hormone administration on posthepatectomy liver regeneration were not obvious; 2) combined administration of insulin and glucagon increased the weight of the remnant liver, the DNA content, and the rate of DNA synthesis; 3) the combined administration of insulin, glucagon, and EGF increased the regeneration based on the remnant liver weight and mitotic index; and 4) there was no concordance between the change in blood glucose levels and the effect of hormones during liver regeneration.
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PMID:Rat liver regeneration after partial hepatectomy: effects of insulin, glucagon and epidermal growth factor. 136 Feb 95

Upon epidermal growth factor (EGF) stimulation, fetal (20 days of gestation) and regenerating (44-48 h after partial hepatectomy) rat hepatocytes, isolated and cultured under identical conditions, increased DNA synthesis and entered into S-phase and mitosis, measured as [3H]thymidine incorporation and DNA content per nucleus in a flow cytometer, respectively. Fetal hepatocytes consisted of a homogeneous population of diploid (2C) cells. Two different populations of cells were present in regenerating liver, diploid (2C) and tetraploid (4C) cells, that responded to EGF. Glucagon or norepinephrine did not affect EGF stimulation of DNA synthesis in fetal liver cells, but they potentiated EGF response in regenerating hepatocyte cultures. Glucocorticoid hormones (dexamethasone) inhibited DNA synthesis in fetal hepatocyte cultures, an effect potentiated by the presence of glucagon or norepinephrine. In contrast, in regenerating hepatocytes, dexamethasone increased EGF-induced proliferation. EGF-dependent DNA synthesis was inhibited by TGF-beta in both fetal and regenerating cultured hepatocytes. TGF-beta action was partially suppressed by norepinephrine in regenerating hepatocytes, but was without effect in fetal hepatocyte cultures, whereas a synergistic action between TGF-beta and dexamethasone inhibiting growth in fetal but not in regenerating hepatocytes was found. Taken together, these results may suggest that there are significant differences between fetal and regenerating hepatocyte growth in their response to various hormones.
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PMID:Differential proliferative response of cultured fetal and regenerating hepatocytes to growth factors and hormones. 139 1

We investigated the changes in cell surface epidermal growth factor (EGF) receptors in the liver after partial hepatectomy, and in primary adult rat hepatocyte cultures following stimulation with either EGF, or a preparation of hepatocyte growth factor, or an insulin-glucagon combination. We confirmed a reduction in EGF receptors on hepatocytes after partial hepatectomy and a rapid down-regulation of EGF receptors on normal hepatocytes in vitro following exposure to EGF. Insulin and glucagon and hepatocyte growth factor, whilst initiating hepatocyte DNA synthesis, had only slight effects on their EGF binding capacity and EGF-receptor affinity. These results indicate that changes in cell membranes early in proliferation have only non-specific effects on EGF receptors, and, therefore, support the role of ligand binding to the EGF receptor as an important component of hepatocyte proliferation in vivo.
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PMID:Comparative effects of epidermal growth factor, an insulin-glucagon combination, and a hepatocyte growth factor preparation on epidermal growth factor receptors. 150 26

The effect of epidermal growth factor (EGF) on liver regeneration was investigated in rats subjected to partial hepatectomy. In a dose-response study EGF in doses of 6 and 24 nmol/kg x day increased liver regeneration after treatment for 48 h compared with controls, whereas a dose of 48 nmol/kg x day had no effect. In a subsequent study EGF, 6 nmol/kg x day, accelerated liver regeneration significantly after 36, 48, and 72 h of treatment. A possible influence of EGF on other hepatotrophic factors was investigated. No changes in the concentration of gastrin, insulin, or glucagon was found in portal venous blood. This study has shown that EGF in small doses can stimulate liver regeneration, whereas higher doses are ineffective. The study suggests that EGF should be regarded as a hepatotrophic factor.
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PMID:Stimulatory effect of epidermal growth factor on liver regeneration after partial hepatectomy in rats. 152 71

Lipoprotein lipase and hepatic lipase are members of the lipase gene family sharing a high degree of homology in their amino acid sequences and genomic organization. We have recently shown that isolated hepatocytes from neonatal rats express both enzyme activities. We show here that both enzymes are, however, differentially regulated. Our main findings are: (i) fasting induced an increase of the lipoprotein lipase activity but a decrease of the hepatic lipase activity in whole liver, being in both cases the vascular (heparin-releasable) compartment responsible for these variations. (ii) In isolated hepatocytes, secretion of lipoprotein lipase activity was increased by adrenaline, dexamethasone and glucagon but was not affected by epidermal growth factor, insulin or triiodothyronine. On the contrary, secretion of hepatic lipase activity was decreased by adrenaline but was not affected by other hormones. (iii) The effect of adrenaline on lipoprotein lipase activity appeared to involve beta-adrenergic receptors, but stimulation of both beta- and alpha 1-receptors seemed to be required for the effect of this hormone on hepatic lipase activity. And (iv), increased secretion of lipoprotein lipase activity was only observed after 3 h of incubation with adrenaline and was blocked by cycloheximide. On the contrary, decreased secretion of hepatic lipase activity was already significant after 90 min of incubation and was not blocked by cycloheximide. We suggest that not only synthesis of both enzymes, but also the posttranslational processing, are under separate control in the neonatal rat liver.
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PMID:Lipoprotein lipase and hepatic lipase activities are differentially regulated in isolated hepatocytes from neonatal rats. 156 12

This study used 10-nm gold particles with 5-7 insulin molecules attached (Au10-Ins) to investigate the site of interaction of insulin with the nuclear envelope during insulin uptake into intact isolated nuclei. Despite its size, and in the absence of ATP, Au10-Ins entered nuclei through the nuclear pore and associated with the heterochromatin. Because Au10-Ins is essentially gold-bovine serum albumin (Au-BSA) with a few insulin molecules attached, the effect of insulin and other growth factors on the nuclear accumulation of BSA coupled to 10-, 15-, and 24-nm-diam colloidal gold particles (Au10-BSA, Au15-BSA, and Au24-BSA) was determined. The Au-BSA complexes were excluded from nuclei in the absence of insulin. Insulin (0.5-100 ng/ml) caused a dose-dependent accumulation of Au10-BSA in the nucleus. The nuclear membrane was shown to be intact by several criteria, therefore, accumulation of Au-BSA occurred via the nuclear pore and was not due to leakage across or through the membrane. Uptake of 15- and 24-nm Au-BSA molecules was not affected by insulin, suggesting the hormone had a limited effect in increasing the functional diameter of the nuclear pores. Glucagon, epidermal growth factor, platelet-derived growth factor, insulinlike growth factor I, and insulin A or B chains did not stimulate the accumulation of Au10-BSA. The insulin-stimulated accumulation of Au10-BSA was blocked by concanavalin A, mimicked by wheat-germ agglutinin, and did not require ATP. The Au10-BSA in the nucleus was associated with heterochromatin, suggesting it bound to a nuclear element.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin stimulates accumulation and efflux of macromolecules in isolated nuclei from H35 hepatoma cells. 173 9

Multiple rounds of cell division were induced in primary cultures of rat hepatocytes in serum-free medium containing 10 mmol/L nicotinamide and 10 ng epidermal growth factor/ml. Cells per culture almost doubled between day 1 and day 5. The proliferating cells were predominantly mononucleate. The time course of DNA synthesis in cultured hepatocytes showed that peaks of the incorporation of 3H-thymidine were observed at 60 hr and 82 hr after plating. Labeling indices of the cells indicated that almost half the cells were labeled with 3H-thymidine in the periods 48 to 72 hr and 72 to 96 hr after plating. In addition, about 20% of the hepatocytes in culture initiated a second round of the cell cycle between 48 and 96 hr in culture, as demonstrated by the use of continuous treatments with 3H-thymidine and 5-bromo-2'-deoxyuridine. Furthermore, by day 4 of culture, about 40% and 15% of metaphases resulted from a second and third round of cell division, respectively. The cultured hepatocytes on day 5 stained with albumin immunocytochemically, and the activity of tyrosine aminotransferase was induced by dexamethasone and glucagon on day 3. In addition, electron micrographs revealed that dividing cells not only had many characteristics of liver mitochondria and bile canaliculus-like structures, but many also contained a few large peroxisomes with internal crystalline nucleoids.
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PMID:Multiple cell cycles occur in rat hepatocytes cultured in the presence of nicotinamide and epidermal growth factor. 182 39

The effect of ethanol on receptor-mediated phospholipase C-linked signal transduction processes was investigated in isolated rat hepatocytes. Pretreatment of the cells with ethanol (6-300 mM) markedly inhibited a subsequent stimulation of phospholipase C by vasopressin, angiotensin II, or epidermal growth factor. By contrast, the effects of the alpha 1-adrenergic agonist phenylephrine and of glucagon were not affected by ethanol pretreatment. Ethanol inhibited the agonist-induced decrease in polyphosphoinositides, the formation of inositol phosphates, and the increase in cytosolic free Ca2+ levels, as detected with the intracellular Ca2+ indicator indo-1. The effects of ethanol were concentration dependent and were pronounced at low concentrations of agonists but were not significant at saturating levels. Pretreatment of the cells with the protein kinase C inhibitor H7 partly prevented the inhibition by ethanol of vasopressin-induced phospholipase C activation. By contrast, pretreatment of the cells with (Rp)-adenosine cyclic 3':5'-phosphorothioate [Rp)-cAMP-S), a competitive inhibitor of protein kinase A, potentiated the inhibitory effect of ethanol on the Ca2+ mobilization by vasopressin. (Rp)-cAMP-S similarly potentiated the inhibition of phospholipase C by the protein kinase C-activating phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). The kinase A inhibitor also made the Ca2+ mobilization by phenylephrine sensitive to ethanol, indicating that the formation of cAMP in the cells played a role in suppressing the sensitivity to ethanol. Pretreatment of the cells with ethanol enhanced the inhibitory effects of TPA on the vasopressin-induced phospholipase C activation at all concentrations of the hormone; however, these synergistic effects were prevented when TPA was added prior to ethanol, a condition that prevents the activation of phospholipase C by ethanol. The data indicate that ethanol causes desensitization of the receptor-mediated phospholipase C secondary to the ethanol-induced activation of phospholipase C and activation of protein kinase C. Ethanol treatment also affects the sensitivity of the phospholipase C system to control by protein kinases A and C. The data indicate that ethanol can affect the control of intracellular signal transduction processes in liver cells under physiologically relevant conditions.
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PMID:Ethanol causes desensitization of receptor-mediated phospholipase C activation in isolated hepatocytes. 184 16

Polypeptide hormones and growth factors bind to cell surface receptors and are internalized by receptor-mediated endocytosis. Both [125I]insulin and [125I]epidermal growth factor (EGF) are internalized to a much greater extent than [125I]glucagon in freshly isolated rat hepatocytes. All three ligands bind initially and preferentially to the microvillous surface of the hepatocyte, but only [125I]insulin and [125I]EGF undergo significant redistribution to the nonvillous surface of the cell. Thus, the degree of lateral mobility of the ligand receptor complex is strongly correlated with the extent of internalization of the ligand. Since the beta-subunit of the insulin and the EGF receptors span the plasma membrane only once and both receptors are autophosphorylated, it is possible that these are important determinants of the receptor mobility.
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PMID:The relationship of ligand receptor mobility to internalization of polypeptide hormones and growth factors. 184 11


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