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)

Hepatocyte growth factor (HGF), a potent mitogen for adult rat hepatocytes in primary culture, has previously been shown to be primarily expressed in the nonparenchymal cells of the liver. Using polyclonal antisera against human and rat HGFs we studied the tissue distribution of HGF immunohistochemically and found the most intense staining in the pancreas islet cells in both man (autopsy cases) and the rat. Differential localization of 4 pancreas islet hormones, glucagon, insulin, somatostatin and pancreatic polypeptide, revealed HGF to be preferentially expressed within the glucagon-positive cells. The results indicate that HGF is primarily produced or stored in A-cells and may act as a growth factor in a paracrine and an endocrine fashion, like various other hormones.
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PMID:Immunohistochemical localization of hepatocyte growth factor protein in pancreas islet A-cells of man and rats. 136 29

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

Combined treatment of thymosin, amino acid, blood products and glucagon-insulin (G-I) for severe viral hepatitis reduced the death rate to 42.11-54.54% in the years from 1983 to 1985. Since 1986, 207 patients with severe viral hepatitis have been treated in our department, 80 of them died (38.6%). All of the patients were divided into 6 groups receiving different therapeutic measures. Group 1 and 2 received different combinations of the above-mentioned drugs; group 3,4,5 and 6 were given fetal liver cell suspension, hepatocyte growth factor (HGF), Chinese traditional medicine and prostaglandin E1 (PGE1) either alone or in combination with other medications. Therapeutic results were better in group 3,4,5 and 6 than in group 1 and 2. Determination of the activity of tumor necrosis factor (TNF) showed that it was higher in the patients than in the control subjects. TNF activity was increased in rats with experimental liver failure; HGF and PGE1 can protect experimental liver necrosis and reduce the serum TNF activity.
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PMID:[Treatment of severe viral hepatitis]. 153 36

Completely diverting portacaval shunt (Eck's fistula) in dogs causes hepatocyte atrophy, disruption of hepatocyte organelles, fatty infiltration and low-grade hyperplasia. The effect of hepatic growth regulatory substances on these changes was assessed by constantly infusing test substances for four postoperative days after Eck's fistula into the detached left protal vein above the shunt. The directly infused left lobes were compared histopathologically with the untreated right lobes. In what has been called an hepatotrophic effect, stimulatory substances prevented the atrophy and increased hepatocyte mitoses. Of the hormones tested, only insulin was strongly hepatotrophic; T3 had a minor effect, and glucagon, prolactin, angiotensin II, vasopressin, norepinephrine and estradiol were inert. Insulin-like growth factor, hepatic stimulatory substance, transforming growth factor-alpha and hepatocyte growth factor (also known as hematopoietin A) were powerfully hepatotrophic, but epidermal growth factor had a barely discernible effect. Transforming growth factor-beta was inhibitory, but tamoxifen, interleukin-1 and interleukin-2 had no effect. The hepatotrophic action of insulin was not altered when the insulin infusate was mixed with transforming growth factor-beta or tamoxifen. These experiments show the importance of in vivo in addition to in vitro testing of putative growth control factors. They illustrate how Eck's fistula model can be used to screen for such substances and possibly to help delineate their mechanisms of action.
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PMID:Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula. 191 68

We report further characterisation of the hepatocyte growth factor 'hepatotropin' which is found in rat serum 24 h after partial hepatectomy. Hepatotropin enhances DNA synthesis in primary cultures of adult rat hepatocytes, and is of high molecular weight. Serum fractions were separated by gel filtration, heparin-sepharose affinity chromatography and ion-exchange chromatography. Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) identified a band of apparent subunit relative molecular weight (Mr) 100,000 associated with biological activity, although purification to homogeneity has not been achieved. The activity is heat-labile, trypsin-sensitive, and stable to lyophilisation, but loses activity after dilution and reconcentration. In combination with known peptide hepatocyte growth modulators, hepatotropin acted synergistically with insulin and epidermal growth factor (EGF) but its action was not enhanced by glucagon. Studies on isolated rat hepatocyte membranes showed no evidence of enhanced phosphorylation of the EGF receptor by hepatotropin. The relationship of hepatotropin to previously described serum and platelet-derived growth factors is discussed.
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PMID:Further characterisation of 'hepatotropin', a high molecular weight hepatotrophic factor in rat serum. 268 95

The effect of recombinant human hepatocyte growth factor (h-rHGF), a potent mitogen for hepatocytes, was investigated in primary cultures of human hepatocytes. Here, we describe a series of experiments to investigate the kinetics of its mitogenic action, as well as its metabolic effects on cultured human hepatocytes. The h-rHGF is a potent signal for initiating DNA synthesis in human hepatocytes, with maximal stimulatory effects at 10 ng/mL (0.1 pmol/L). The kinetics of DNA synthesis showed a lag of about 48 to 72 hours, followed by a maximum at 96 hours. At least 48 hours of continuous exposure to h-rHGF are required to initiate DNA synthesis in quiescent human hepatocytes. Cell cycle analysis by flow cytometry showed that most of quiescent 2c cells have left G0/G1 and entered the cell cycle (S and G2/M phases) by 96 hours of continuous exposure to h-rHGF. When compared with other growth factors, h-rHGF was a much more potent mitogen. The effects of 10 ng/mL (0.1 pmol/L) h-rHGF on DNA synthesis were only achieved by 1.5 pmol/L epidermal growth factor (EGF), 0.1 mumol/L insulin, or 1 mumol/L glucagon. It is noteworthy that the effect of h-rHGF was potentiated by glucagon but not by insulin or EGF. The stimulatory effect of HGF on DNA synthesis was gradually inhibited by h-rHGF transforming growth factor beta (TGF-beta) in the range 1 to 10 ng/ml. The HGF also influenced the expression of other hepatic genes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of hepatocyte growth factor on the growth and metabolism of human hepatocytes in primary culture. 773 30

Transforming growth factor alpha (TGF alpha) is supposed to act as a mitogen for hepatocytes in an autocrine manner in vitro and in vivo. Retarded liver regeneration is a possible reason for poor prognosis of fulminant hepatitis (FH). We analyzed serum TGF alpha levels in patients with FH and patients with acute nonfulminant hepatitis (AH). Also, the relation of those levels to serum hepatocyte growth factor (HGF) levels and their changes after glucagon-insulin (G-I) therapy were studied. Maximal serum TGF alpha levels achieved in each case after admission until recovery from disease or death were correlated positively with maximal serum alanine transaminase (ALT) and total bilirubin levels in patients with AH, but negatively with maximal total bilirubin levels in patients with FH. Maximal serum TGF alpha levels in patients with FH were significantly higher in survivors than in nonsurvivors. Maximal serum HGF levels were positively correlated with maximal serum TGF alpha levels in patients with AH, but not in patients with FH. Multiple regression analysis indicated that G-I therapy was related to the increment of serum TGF alpha levels in patients with FH. These results suggest that serum TGF alpha levels are increased in accordance with liver regeneration after necrosis in patients with AH, but such liver regeneration may be retarded, depending on the extent of liver damage in patients with FH. G-I therapy seems to stimulate liver regeneration after liver damage. The possible contribution of TGF alpha and HGF to liver regeneration merits consideration for recovery from AH.
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PMID:Liver regeneration in fulminant hepatitis as evaluated by serum transforming growth factor alpha levels. 859 49

Pancreatic AR42J cells are derived from acinar cells and express both exocrine and neuroendocrine properties. We have recently shown that these cells convert into insulin-producing cells in vitro after treatment with activin A and betacellulin. Here, we investigated the effect of hepatocyte growth factor (HGF) in those cells. When AR42J cells were incubated with HGF, DNA synthesis was attenuated, and the amylase content was reduced in a concentration-dependent manner. HGF-treated cells extended processes, but bundle formation was not observed using an antibody against tubulin. Reverse both insulin and pancreatic polypeptide (PP) were expressed in HGF-treated, but not naive, AR42J cells. Immunocytochemical analysis indicated that approximately 3% of the HGF-treated cells were stained with antiinsulin antibody, and some were also stained with anti-PP antibody. When AR42J cells were exposed to a combination of activin A and HGF, cells extended longer processes, and over 10% of them were stained with antiinsulin antibody. In these cells, messenger RNAs for insulin, PP, glucose transporter 2, and glucokinase, but not those for glucagon or somatostatin, were expressed. A subclone of AR42J cells, AR42J-B13, was obtained. Most of the AR42J-B13 cells converted to insulin-producing cells after the incubation with activin A and HGF. Insulin secretion was augmented by tolbutamide, depolarizing concentrations of potassium, carbachol, and glucagon-like peptide-1 in these cells. These results indicate that HGF reduces the acinar cell-like property of AR42J cells and converts them into insulin-producing cells. The effect of HGF was markedly enhanced by activin A.
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PMID:Formation of insulin-producing cells from pancreatic acinar AR42J cells by hepatocyte growth factor. 875 73

Ex vivo expansion of human fetal pancreatic endocrine cells is important for biological studies and as a potential tissue source for transplantation in insulin-deficient states. In tissue culture experiments involving the use of hepatocyte growth factor/scatter factor and selected extracellular matrices, we obtained a 30-fold increase in cell number of human fetal pancreatic epithelial cells. This proliferation in monolayer culture was associated with marked downregulation of insulin and glucagon gene expression. However, gene expression increased when the cells were combined into three-dimensional aggregates, suggesting that cell-cell contact mediated mechanisms regulate the transcription of islet-specific genes, a process enhanced by nicotinamide (NIC). After transplantation into nude mice, either as cell suspensions or aggregates, only the cell aggregates treated with NIC developed into mature functional islet-like structures. These are the first experiments to describe the interactions of specific matrices and growth factors in the ex vivo expansion of human fetal pancreatic cells, and they also show the importance of cell aggregates in the context of cellular and molecular events that might positively influence islet cell transplantation.
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PMID:Regulation of proliferation and differentiation of human fetal pancreatic islet cells by extracellular matrix, hepatocyte growth factor, and cell-cell contact. 877 26

Phosphatidylinositol 3-kinase (PI3K) has been shown to be an important mediator of intracellular signal transduction in mammalian cells. We show here, for the first time, that the blockade of PI3K activity in human fetal undifferentiated cells induced morphological and functional endocrine differentiation. This was associated with an increase in mRNA levels of insulin, glucagon, and somatostatin, as well as an increase in the insulin protein content and secretion in response to secretagogues. Blockade of PI3K also increased the proportion of pluripotent precursor cells coexpressing multiple hormones and the total number of terminally differentiated cells originating from these precursor cells. We examined whether any of the recently described modulators of endocrine differentiation could participate in regulating PI3K activity in fetal islet cells. The activity of PI3K was inversely correlated with the hepatocyte growth factor/scatter factor-induced downregulation or nicotinamideinduced upregulation of islet-specific gene expression, giving support to the role of PI3K, as a negative regulator of endocrine differentiation. In conclusion, our results provide a mechanism for the regulation of hormone-specific gene expression during human fetal neogenesis. They also suggest a novel function for PI3K, as a negative regulator of cellular differentiation.
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PMID:Phosphatidylinositol 3-kinase is a negative regulator of cellular differentiation. 916 12


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