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 effect of activin-A on glycogenolysis was studied in isolated rat hepatocytes. Activin-A stimulated glucose output in hepatocytes in a dose-dependent manner. The maximal effect of the glycogenolytic action of activin-A, which was about 50% of the glucagon action, was obtained at 10(-9) M. When 10(-9) M activin-A and 5 x 10(-9) M glucagon were added simultaneously, the actions of these two agents were additive. In contrast, there was no additivity when 10(-9) M activin-A and 10(-8) M angiotensin-II were added. Activin-A did not increase cAMP at any doses tested, but induced a rapid increase in cytoplasmic free calcium concentration. Activin-A increased the cytoplasmic free calcium concentration even in the presence of 1 microM extracellular calcium, suggesting that activin-A caused calcium release from an intracellular calcium pool(s). The internal calcium pool affected by activin-A appeared to be the same as that affected by either angiotensin-II or vasopressin. When [3H] inositol-labeled hepatocytes were incubated with activin-A, radioactivity in the inositol trisphosphate fraction was rapidly increased. These results indicate that activin-A acts on rat hepatocytes and stimulates glycogenolysis by activating the calcium messenger system.
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PMID:Stimulation of glucose production by activin-A in isolated rat hepatocytes. 254 39

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, a member of the transforming growth factor-beta supergene family, stimulates insulin secretion in rat pancreatic islets and causes glycogenolysis in isolated rat hepatocytes. These observations prompted us to determine whether activin-A existed in rat pancreas by using an immunocytochemical method. Cells in pancreatic islets were stained by antibody against activin-A, whereas no immunoreactivity was observed in exocrine pancreas. Cells localized in the mantle of the islets were densely stained by the antibody. Immunoelectron microscopic study showed that activin-A existed in secretory granules in both A- and D-cells. Furthermore, studies using a double labeling method revealed that activin-A coexisted with glucagon in secretory granules in A-cells and with somatostatin in D-cells. Antibody against inhibin-A weakly stained cells in both the core and mantle of the islets only when the rat was pretreated with colchicine. Subtypes of activin subunit in islets were identified to be beta A by a reverse transcription-polymerase chain reaction method. In addition, mRNA for inhibin alpha-subunit was expressed in islets. However, mRNA for these inhibin subunits was not detected in exocrine pancreas. To further examine the action of activin-A on insulin secretion, we examined the effect of activin-A in a flow-through perifusion system. Activin-A induced a biphasic insulin secretory response in the presence of 2.8 mM glucose, and a low concentration of activin-A, which does not stimulate insulin secretion by itself, markedly enhanced glucose-mediated insulin secretion at concentrations above 2.8 mM glucose. Inhibin-A did not affect insulin secretion. These results suggest the existence of activin-A in A- and D-cells of rat pancreatic islets and raise the possibility that activin-A acts as a physiological regulator of carbohydrate metabolism.
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PMID:Existence of activin-A in A- and D-cells of rat pancreatic islet. 834 2

We first detected the mRNA expression of follistatin and three subunits of inhibin/activin in rat pancreatic islets by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry using anti-follistatin serum (against residues 123-134) revealed that follistatin was localized only in insulin-producing B cells. Although the beta A subunit was detectable in the islets, the immunostainable cell types were completely different with two beta A antisera, i.e. anti-beta A (1-10)-Tyr stained B cells, while anti-beta A (87-99) stained glucagon-producing A cells. This inconsistent immunoreactivity was probably related to follistatin binding to beta subunits of inhibin/activin. This study indicates that follistatin and inhibin/activin in the islet serve as paracrine or autocrine modulators in the endocrine pancreas.
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PMID:Expression of alpha, beta A and beta B subunits of inhibin or activin and follistatin in rat pancreatic islets. 845 12

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 member of the transforming growth factor-beta superfamily, has been shown to be a critical regulator in exocrine and endocrine pancreas formation. The purpose of our study was to describe the ontogeny of activin B and its inhibitor, follistatin, in developing pancreas and to elucidate potential mechanisms for exocrine and endocrine lineage selection. Mouse embryonic pancreata were dissected at various ages (day 10 [E10.5] to birth [E18.5]), sectioned, and immunostained for activin B (one of two existing isomers, A and B), follistatin, insulin, and glucagon. In addition, reverse transcriptase-polymerase chain reaction was employed to determine the messenger RNA expression of follistatin in isolated pancreatic epithelia and mesenchyme of various ages. Activin B was first detected at E12.5 in epithelial cells coexpressing glucagon. At E16.5 these coexpressors appeared as clusters in close proximity to early ducts. By E18.5 activin B was localized to forming islets where cells coexpressed glucagon and were arranged in the mantle formation characteristic of mature alpha cells. Follistatin was found to be ubiquitous in pancreatic mesenchyme at early ages by immunohistochemical analysis, disappearing sometime after E12.5. Follistatin reappeared in E18.5 islets and remains expressed in adult islets. Follistatin messenger RNA was first detected in epithelium at E11.5, preceding its protein expression in islets later in gestation. We propose that mesenchyme-derived follistatin inhibits epithelium-derived activin at early embryonic ages allowing for unopposed exocrine differentiation and relative suppression of endocrine differentiation. At later ages the decrease in the amount of mesenchyme relative to epithelium and the subsequent drop in follistatin levels liberates epithelial activin to allow differentiation of endocrine cells to form mature islets by the time of birth.
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PMID:Ontogeny of activin B and follistatin in developing embryonic mouse pancreas: implications for lineage selection. 1076 89

In the present study, isolated presumptive ectoderm from Xenopus blastula was treated with activin and retinoic acid to induce differentiation into pancreas. The presumptive ectoderm region of the blastula consists of undifferentiated cells and is fated to become epidermis and neural tissue in normal development. When the region is isolated and cultured in vitro, it develops into atypical epidermis. Isolated presumptive ectoderm was treated with activin and retinoic acid. The ectoderm frequently differentiated into pancreas-like structures accompanied by an intestinal epithelium-like structure. Sections of the explants viewed using light and electron microscopy showed some cells clustered and forming an acinus-like structure, including secretory granules. The pancreas-specific molecular markers insulin and XIHbox8 were also expressed in the treated explants. The pancreatic hormones, insulin and glucagon, were detected in the explants using immunohistochemistry. Therefore, sequential treatment with activin and retinoic acid can induce presumptive ectoderm to differentiate into a morphological and functional pancreas in vitro. When ectoderm was immediately treated with retinoic acid after treatment with activin, well-differentiated pronephric tubules were seen in a few of the differentiated pancreases. Treatment with retinoic acid 3-5 h after activin treatment induced frequent pancreatic differentiation. When the time lag was longer than 15h, the explants developed into axial mesoderm and pharynx. The present study provides an effective system for analyzing pancreas differentiation in vertebrate development.
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PMID:In vitro pancreas formation from Xenopus ectoderm treated with activin and retinoic acid. 1114 81

It is currently believed that pancreatic progenitor or stem cells exist in the ductal cell population and that these cells have the ability to be grown and differentiated into endocrine cells for the treatment of diabetes. In this study, we have examined this potential in IMPAN (Immortalized Pancreatic) cells. These cells are derived from the adult H-2K(b)-tsA58 transgenic mouse. We observed an increased mRNA expression of insulin, proendocrine gene neurogenin 3, and beta-cell transcription factor Pdx1 when the cells were grown on bovine collagen I gels. The induction profile of these three genes was similar under the tested conditions. No glucagon or other endocrine-specific transcription factors were detectable. Application of GIP, GLP-1 derivative NN2211, and activin-A/betacellulin to IMPAN cells in normal culture did not lead to endocrine differentiation. In conclusion, it appears that the ability of IMPAN cells to mature to endocrine cells is limited.
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PMID:IMPAN cells: a pancreatic model for differentiation into endocrine cells. 1169 65

As activin is believed to be a key signalling factor during early pancreatic development, its influence on the proliferation and/or determination of insulin cells in the developing chick dorsal pancreatic bud was investigated. Dorsal pancreatic buds of 5-day-old chick embryos were explanted on to Matrigel and cultured in serum-free medium (Ham's F12.ITS), to which 1 or 10ng/ml activin was added. After 7 days in culture, the explants were processed for immunocytochemistry and the insulin-positive cells were scored and expressed as a proportion of the sum of insulin and glucagon cells. When compared to the control cultures (Hams F12.ITS alone), activin treatment resulted in respective increases in the proportion of insulin cells of 1.6 and 1.9 fold. It is suggested that activin treatment favours differentiation of the insulin cell pathway relative to glucagon cells.
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PMID:Exogenous activin increases the proportion of insulin cells in the developing chick pancreas in culture. 1246 81

During embryonic development, organs arise along the gut tube as a series of buds in a stereotyped anterior-posterior (A-P) pattern. Using chick-quail chimeras and in vitro tissue recombination, we studied the interactions governing the induction and maintenance of endodermal organ identify focusing on the pancreas. Though several permissive signals in pancreatic development have been previously identified, here we provide evidence that lateral plate mesoderm sends instructive signals to the endoderm, signals that induce expression of the pancreatic genes Pdx1, p48, Nkx6.1, glucagon, and insulin. Moreover, this instructive signal directs cells to form ectopic insulin-positive islet-like clusters in endoderm that would otherwise form more rostral organs. Once generated, endocrine cells no longer require interaction with mesoderm, but nonendocrine cells continue to require permissive signals from the mesoderm. Stimulation of activin, BMP, or retinoic acid signaling is sufficient to induce Pdx1 expression in endoderm anterior to the pancreas. Lateral plate mesoderm appears to pattern the endoderm in a posterior-dominant fashion as first noted in the patterning of the neural tube at the same embryonic stage. These findings argue for a central role of the mesoderm in coordinating the A-P pattern of all three primary germ layers.
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PMID:Signals from lateral plate mesoderm instruct endoderm toward a pancreatic fate. 1281 92


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