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 present study was conducted to examine an involvement of G protein in the action of activin A in rat parenchymal liver cells. Activin A induced a dose-dependent increase in inositol phosphates in cells prelabelled with [3H]inositol. The effect of activin A was completely blocked by pretreatment of the cells with pertussis toxin. In contrast, pertussis toxin had little effect on angiotensin II-induced production of inositol phosphates. Both activin A and angiotensin II inhibited glucagon-mediated production of cAMP. Pretreatment of the cells with pertussis toxin blocked the inhibition induced by both activin A and angiotensin II. In permeabilized cells, activin A augmented production of inositol phosphates. Activin-mediated production of inositol trisphosphate was enhanced by GTP-gamma S and was attenuated by GDP-beta S. These results suggest that a pertussis toxin-sensitive G protein(s) may be involved in the action of activin A in hepatocytes.
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PMID:Pertussis toxin blocks activin A-induced production of inositol phosphates in rat hepatocytes. 132 3

Expression of activin A in fetal rat pancreas was studied immunohistochemically by using anti-activin A antibody. On embryonic day 12 (E12), cells in cap-like pancreatic anlage were stained with anti-activin A antibody. In these sections, no immunoreactive insulin or glucagon was observed. On E13.5, cells containing immunoreactive activin A were observed in pancreatic anlage. These cells were also stained by both anti-glucagon and anti-insulin antibodies. On E15, a cluster of cells could be recognized as a primitive islet. In the primitive islet, cells containing immunoreactive activin A were observed. Activin-positive cells were located mainly in the mantle of the primitive islet but some were located in the core of the primitive islet. These activin-positive cells also expressed glucagon. Among them, cells also containing insulin were observed. In addition to activin-positive cells, cells containing only insulin were detected in the core of the primitive islet. These results indicate that immunoreactive activin A is expressed in fetal pancreas. The expression of activin A is an early event during the development of pancreatic endocrine cells.
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PMID:Expression of immunoreactive activin A in fetal rat pancreas. 759

Activin A now used as a recombinant product was first isolated from ovarian fluid. Its effects on insulin and glucagon secretion, 45Ca2+ net uptake, 86Rb+ efflux and inositol-trisphosphate (Ins-1,4,5-P3) content were investigated in rat pancreatic islets. Activin A increased insulin secretion at either 3.0, 8.3 or 16.7 mM glucose. It decreased glucagon secretion at 3.0, had no effect at 8.3 and increased glucagon secretion at 16.7 mM glucose. The effect on insulin release was concentration dependent; effects were obvious at 1 and 10 nM activin A. The effect on insulin release was paralleled by an effect on 45Ca2+ net uptake. 10 nM activin A were effective in elevating Ins-1,4,5-P3 content at either glucose concentration used. 86Rb+ efflux as an indicator for closing K+ channels which leads to a depolarization of the beta-cell membrane and which is a prerequisite for Ca++ influx was inhibited by activin A at a low glucose concentration (3.0 mM). The data indicate that the new peptide activin A elevates insulin release at various glucose concentrations: at low and high glucose concentrations 45Ca2+ uptake is involved. At low glucose concentrations inhibition of 86Rb+ efflux is a prerequisite sufficient to lead to a depolarization and subsequent Ca++ uptake; accumulation of Ins-1,4,5-P3 probably helps mediating the insulinotropic effect by additionally elevating intracellular Ca++.
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PMID:Activin A: its effects on rat pancreatic islets and the mechanism of action involved. 836 69

Rat pancreatic AR42J cells possess exocrine and neuroendocrine properties. Activin A induces morphological changes and converts them into neuron-like cells. In activin-treated cells, mRNA for pancreatic polypeptide (PP) but not that for either insulin or glucagon was detected by reverse transcription-PCR. About 25% of the cells were stained by anti-PP antibody. When AR42J cells were incubated with betacellulin, a small portion of the cells were stained positively with antiinsulin and anti-PP antibodies. The effect of betacellulin was dose dependent, being maximal at 2 nM. Approximately 4% of the cells became insulin positive at this concentration, and mRNAs for insulin and PP were detected. When AR42J cells were incubated with a combination of betacellulin and activin A, approximately 10% of the cells became insulin positive. Morphologically, the insulin-positive cells were composed of two types of cells: neuron-like and round-shaped cells. Immunoreactive PP was found in the latter type of cells. The mRNAs for insulin, PP, glucose transporter 2, and glucokinase, but not glucagon, were detected. Depolarizing concentration of potassium, tolbutamide, carbachol, and glucagon-like peptide-1 stimulated the release of immunoreactive insulin. These results indicate that betacellulin and activin A convert amylase-secreting AR42J cells into cells secreting insulin. AR42J cells provide a model system to study the formation of pancreatic endocrine cells.
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PMID:Betacellulin and activin A coordinately convert amylase-secreting pancreatic AR42J cells into insulin-secreting cells. 860 30

Activin A is a multifunctional protein known to stimulate insulin secretion (Yasuda H et al., (1993) Endocrinology 133, 624-630). The present study was conducted to determine whether activin A augments insulin secretion in the absence of ambient glucose. In the presence of 2.7 mM glucose, and 1.25 mM calcium, activin A induced a biphasic secretory response of insulin. In the absence of glucose in perifusate, activin A induced a small but significant release of insulin. The effect of activin A was monophasic in the absence of glucose. In contrast, glucagon-like peptide-1 (GLP-1) had no effect on insulin secretion under the same conditions. However, GLP-1 could enhance insulin secretion induced by activin A in glucose-free medium. Activin A induced a transient increase in cytoplasmic-free calcium concentration, [Ca2+]c, in a fura-2-loaded islet superfused with glucose-free buffer. Again, GLP-1 was without effect on [Ca2+]c by itself in glucose-free buffer. In the presence of activin A, however, GLP-1 could induce an elevation of [Ca2+]c. Finally, GLP-1, but not activin A, increased cAMP content in islets incubated in glucose-free medium. These results indicate that activin A, but not GLP-1, induces insulin secretion in glucose-free medium. Activin A is able to reproduce partly the effect of glucose to support the action of GLP-1 in glucose-free medium.
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PMID:Initiation of insulin secretion in glucose-free medium by activin A. 867 16

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

To elucidate the regulation of follistatin production in the liver, we studied changes in steady-state follistatin mRNA levels in cultured rat hepatocytes. Activin A stimulated follistatin mRNA levels in a time- and concentration-dependent manner. The stimulatory effect of activin A on follistatin mRNA was significant at 2 h, maximal at 6 h and declined thereafter. Incubating the cells with EGF increased follistatin mRNA levels at 48 h and later. The EGF-induced increase in follistatin mRNA was markedly inhibited by exogenous follistatin in the culture medium, which blocks the action of activin A synthesized in hepatocytes, suggesting that endogenous activin A at least partly mediated the effect of EGF. We also examined the effects of transforming growth factor-beta (TGF-beta), glucagon and alpha-adrenergic agonist, phenylephrine, on follistatin mRNA levels. TGF-beta increased the follistatin mRNA to levels similar to those caused by activin A. Phenylephrine and glucagon also increased follistatin mRNA levels but the effects were transient and weaker than those caused by activin A. Finally, follistatin mRNA levels were markedly increased in remnant liver 3 h after 70% hepatectomy. The mRNA remained elevated for up to 72 h. These results indicate that the expression of mRNA for follistatin is positively controlled by activin A, TGF-beta and other hormones or neurotransmitters. The stimulatory effect of EGF on follistatin mRNA is mediated by activin A released from hepatocytes.
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PMID:Regulation of the expression of follistatin in rat hepatocytes. 942 29

AR42J is an exocrine pancreatic cell line that has been reported to differentiate towards an endocrine phenotype when stimulated with various growth factors, such as activin A, hepatocyte growth factor (HGF), betacellulin or glucagon-like peptide 1. In our experiments, AR42J-B13 cells differentiated morphologically in response to the growth factor treatment as reported previously. However, they failed to express the insulin gene. We found that the cells did not express several transcription factors known to be found in the beta-cell, including Nkx6.1, isl-1, Pax4 and Pax6. In addition, the mRNA level for pdx-1 and Nkx2.2 were very low in comparison to the insulinoma cell lines INS-1 and RINm5F. However, some transcription factors typically found in beta-cells and neuroendocrine cells were expressed also in the AR42J-B13 cells. These included BETA2/NeuroD, HNF1alpha, C/EBPbeta and IA-1. Unlike the insulinoma cells, AR42J cells expressed the exocrine transcription factor p48. In order to induce endocrine differentiation, we transfected the AR42J-B13 cells with the full length cDNAs of isl-1, Nkx6.1, Nkx2.2 and pdx-1 under the control of the CMV promoter, both separately and in combinations. The expression of Nkx2.2 led consistently to the appearance of pancreatic polypeptide but not insulin, glucagon or somatostatin mRNA. The PP mRNA expression in Nkx2.2 cDNA transfected cells was independent of the growth factor treatment used for differentiating AR42J cells. In conclusion, the AR42J-B13 line possesses some features of a pancreatic neuroendocrine cell. However, we were unable to confirm the capacity of these cells to differentiate into insulin-producing cells. Our results indicate that Nkx2.2 plays a role in the transcriptional regulation of PP expression.
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PMID:Transcription factor expression and hormone production in pancreatic AR42J cells. 1094 Apr 82

Extracellular signals that guide pancreas cell development are not well characterized. In an in vitro culture system of dissociated pancreas cells from the E15.5 mouse fetus we show that, in the presence of the extracellular matrix protein laminin-1, bone morphogenetic proteins (BMPs-4, -5 and -6) promote the development of cystic epithelial colonies. Transforming growth factor beta1 (TGF-beta1) and activin A antagonise this effect of BMP-6 and inhibit colony formation. Histological analysis revealed that the colonies are composed of E-cadherin-positive epithelial cells, which in localised areas are insulin positive. The colonies also contain occasional glucagon-positive cells, but no somatostatin- or alpha-amylase-positive cells. These findings indicate that members of the TGF-beta superfamily regulate pancreas epithelial cell development and can promote the formation of islet-like structures in vitro.
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PMID:Bone morphogenetic proteins promote development of fetal pancreas epithelial colonies containing insulin-positive cells. 1186 31

beta-Cell transplantation is viewed as a cure for type 1 diabetes; however, it is limited by the number of pancreas donors. Human stem cells offer the promise of an abundant source of insulin-producing cells, given the existence of methods for manipulating their differentiation. We have previously demonstrated that the expression of the beta-cell transcription factor pancreatic duodenal homeobox 1 (PDX-1) in human fetal liver cells activates multiple aspects of the beta-cell phenotype. These cells, termed FH-B-TPN cells, produce insulin, release insulin in response to physiological glucose levels, and replace beta-cell function in diabetic immunodeficient mice. However, they deviate from the normal beta-cell phenotype by the lack of expression of a number of beta-cell genes, the expression of non-beta-cell genes, and a lower insulin content. Here we aimed to promote differentiation of FH-B-TPN cells toward the beta-cell phenotype using soluble factors. Cells cultured with activin A in serum-free medium upregulated expression of NeuroD and Nkx2.2 and downregulated paired box homeotic gene 6 (PAX-6). Glucokinase and prohormone convertase 1/3 were also upregulated, whereas pancreatic polypeptide and glucagon as well as liver markers were downregulated. Insulin content was increased by up to 33-fold, to approximately 60% of the insulin content of normal beta-cells. The cells were shown to contain human C-peptide and release insulin in response to physiological glucose levels. Cell transplantation into immunodeficient diabetic mice resulted in the restoration of stable euglycemia. The cells continued to express insulin in vivo, and no cell replication was detected. Thus, the manipulation of culture conditions induced a significant and stable differentiation of FH-B-TPN cells toward the beta-cell phenotype, making them excellent candidates for beta-cell replacement in type 1 diabetes.
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PMID:Differentiation of human liver-derived, insulin-producing cells toward the beta-cell phenotype. 1612 44


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