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)

Experimental injury is useful to induce tissue stem cells, which may exist in small numbers under normal conditions. The salivary glands originate from the endoderm and consist of acinar and ductal epithelial cells, which have exocrine function. After salivary gland duct ligation, acinar cells disappear as a result of apoptosis, and duct epithelium subsequently proliferates. In this study, we analyzed the tissue stem cells induced by salivary gland duct ligation in mice using immunohistochemistry and flow cytometry. We sorted the Sca-1(+)/c-Kit(+) fraction from adult mice salivary glands by way of fluorescence-activated cell sorting. The sorted cells were apparently homogeneous and were designated mouse salivary gland-derived progenitors (mSGPs). mSGP cells differentiated into a hepatic lineage when cultured in matrigel. In spherical culture in the presence of glucagon-like peptide-1 (GLP-1), these cells differentiated into a pancreatic endocrine lineage. When spheroidal bodies of mSGP, 20 to 30 microm in diameter, were transplanted into liver via the portal vein, the cells integrated into hepatic cords and expressed albumin and alpha1-antitrypsin, suggesting that they had differentiated into hepatic-type cells. Moreover, ductlike structures formed by mSGP cells also appeared, epithelial cells of which were positive for cytokeratin 19. In conclusion, fluorescence-activated cell sorting (FACS) based on histologic evidence is efficient in isolating adult tissue stem cells of the salivary gland. Tissue stem cells of endodermal origin (e.g., hepatic oval cells, pancreatic epithelial progenitor cells, and salivary gland progenitor cells) have similarities in their molecular markers and tissue location. Our findings suggest the existence of common tissue stem cells in endoderm-derived organs.
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PMID:Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages. 1499 85

Stem cell factor (SCF), a progenitor cell growth factor, binds to and activates the c-Kit receptor tyrosine kinase, which is critical for early stem cell differentiation in haematopoiesis and gametogenesis. Nothing is known regarding these interactions during islet development in the human fetal pancreas. The present study was to investigate whether an increase in c-Kit receptor activity in isolated human fetal islet-epithelial clusters, by giving exogenous SCF, would promote beta-cell development. In the intact fetal pancreas, SCF and c-Kit were observed co-localizing with cytokeratin 19 in both ductal and newly forming islet cells. Islet cells isolated from 14 to 16 weeks fetal pancreata were cultured with SCF (50 ng/ml) or vehicle for 48 h. We observed an increase in the number of c-Kit-, pancreatic and duodenal homeobox gene 1- (PDX-1-), insulin- and glucagon-expressing cells in the SCF-treated group (PDX-1 and insulin, p < 0.05). PDX-1 and c-Kit mRNA levels were also up-regulated in the SCF group (PDX-1, p < 0.05), with no change in preproinsulin or proglucagon gene expression. Co-localization of insulin with PDX-1 or c-Kit was observed frequently in SCF-treated cultures. A significantly (p < 0.05) greater proliferative capacity of islet-epithelial clusters was found in the SCF group in parallel with increased (p < 0.02) phosphorylation of Akt in a phosphatidylinositol-3 kinase (PI3K)-dependent manner. Our results demonstrate that SCF/c-Kit interactions are likely to be involved in mediating islet cell differentiation and proliferation during human fetal pancreatic development, and that phosphorylated Akt may have a role downstream of SCF/c-Kit signaling.
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PMID:Stem cell factor/c-Kit interactions regulate human islet-epithelial cluster proliferation and differentiation. 1621 78

The receptor, c-Kit, and its ligand, stem cell factor (SCF), are critical for hematopoietic stem cell differentiation and have been implicated in the development, function, and survival of rodent islets. Previously, we reported that exogenous SCF treatments of cultured human fetal (14-16 wk fetal age) islet-epithelial clusters enhanced islet cell differentiation and proliferation (Li J, Goodyer CG, Fellows F, Wang R. Int J Biochem Cell Biol 38: 961-972, 2006). In the present study, we examined the expression pattern of c-Kit in early to midgestation human fetal pancreata and the relevance of c-Kit receptor tyrosine kinase for insulin gene expression and beta-cell survival. c-Kit is expressed in the intact pancreas in a cell-specific manner, with a significant decrease in immunoreactivity in the duct regions from 8 to 21 wk fetal age, paralleled by a significant increase in expression within endocrine regions. These c-Kit-positive cells are highly proliferative and show frequent coexpression with insulin and glucagon. Treatment of islet-epithelial clusters with anti-ACK45 antibody stimulates c-Kit phosphorylation paralleled by a significant increase in PDX-1 and insulin expression, increased cell proliferation, and reduced beta-cell death. In contrast, transient transfection with c-Kit siRNA results in a three- to fourfold decrease in c-Kit, PDX-1, and insulin expression and decreased cell proliferation. This study describes important changes in the distribution and dynamics of c-Kit-expressing cells during human fetal pancreatic neogenesis, suggesting that c-Kit may be a marker for human pancreatic islet progenitor cells. Functional analysis of the c-Kit receptor tyrosine kinase provides evidence that phosphorylation of c-Kit receptor may be involved in mediating early beta-cell differentiation and survival.
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PMID:Expression of c-Kit receptor tyrosine kinase and effect on beta-cell development in the human fetal pancreas. 1751 80

Pancreatic injury induces replacement of exocrine acinar cells with ductal cells. These ductal cells have the potential to regenerate the pancreas, but their origin still remains unknown. It has been reported that adult pancreatic acinar cells have the potential to transdifferentiate to ductal progenitor cells. In this regards, we established novel adult pancreatic duct-like progenitor cell lines YGIC4 and YGIC5 and assessed the usefulness of these ductal progenitors in the cell therapy of diabetic rats. Acinar cells were cultured from pancreata of male Sprague Dawley rats and gradually attained ductal cell characteristics, such as expression of CK19 and CFTR with a concomitant down-regulation of amylase expression over time, suggesting transdifferentiation from acinar to ductal cells. During cell culture, the expression of Pdx-1, c-Kit, and vimentin peaked and then decreased, suggesting that transdifferentiation recapitulated embryogenesis. Overexpression of pancreas development regulatory genes and CK19, as well as the ability to differentiate into insulin-producing cells, suggests that the YGIC5 cells had characteristics of pancreatic progenitor cells. Finally, YGIC5 cells coexpressing Green fluorescent protein (GFP) and glucagon-like peptide (GLP)-1 under the activation of a zinc-inducible metallothionein promoter were intravenously infused to STZ-induced diabetic rats. Hyperglycemia was ameliorated with elevation of plasma insulin, and GFP-positive donor cells were colocalized in the acinar and islet areas of recipient pancreata following zinc treatment. In conclusion, after establishing pancreatic progenitor cell lines YGIC4 and YGIC5 under the concept of acinar to ductal transdifferentiation in vitro, we demonstrate how these adult pancreatic stem/progenitor cells can be used to regulate adult pancreatic differentiation toward developing therapy for pancreatic disease such as diabetes mellitus.
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PMID:Reversal of diabetes in rats using GLP-1-expressing adult pancreatic duct-like precursor cells transformed from acinar to ductal cells. 1912 29

Recent evidence has shown that stem cell factor (SCF) and its receptor, c-Kit, have an important role in pancreatic islet development by promoting islet cell differentiation and proliferation. In this study, we examined the role of c-Kit and SCF in the differentiation and proliferation of insulin- and glucagon-producing cells using a human pancreatic duct cell line (PANC-1). Our study showed that increased expression of endocrine cell markers (such as insulin and glucagon) and transcription factors (such as PDX-1 and PAX-6) coincided with a decrease in CK19(+) and c-Kit(+) cells (P<0.001) during PANC-1 cell differentiation, determined by immunofluorescence and qRT-PCR. Cells cultured with exogenous SCF showed an increase in insulin(+) (26%) and glucagon(+) (35%) cell differentiation (P<0.01), an increase in cell proliferation (P<0.05) and a decrease in cell apoptosis (P<0.01). siRNA knockdown of c-Kit resulted in a decrease in endocrine cell differentiation with a reduction in PDX-1 and insulin mRNA, as well as the number of cells immunostaining for PDX-1 and insulin. Taken together, these results show that c-Kit/SCF interactions are involved in mediating islet-like cluster formation and islet-like cell differentiation in a human pancreatic duct cell line.
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PMID:c-Kit and stem cell factor regulate PANC-1 cell differentiation into insulin- and glucagon-producing cells. 2053 Dec 94

Although numerous studies of diabetes have focused on cell-mediated immunity to pancreatic islet cells, little is known about immune cells in the pancreatic duct region. In this study, we found that membrane immunoglobulin G (IgG)-positive cells comprised about 1.4% of the total pancreatic cells in mice, forming a thin septum that surrounds large and medium pancreatic ducts. The IgG-positive cells showed low expression of beta-catenin and were amylase-, cytokeratin-, insulin-, and glucagon-negative. Flow cytometric analysis showed that the IgG-positive cells were also positive for CD45, Sca-1, c-Kit, CD49f, and CD133, and negative for Flk-1, suggesting that they were undifferentiated hematopoietic cells. On day 5 after streptozotocin treatment, the percentage of periductal IgG-positive cells increased to 3.37% of total pancreatic cells, and the periductal IgG-positive cells formed multiple layers (beta-catenin-low, and amylase-, cytokeratin-, insulin-, glucagon-negative). These cells were Ki67-negative, suggesting they were recruited from hematopoietic cells. We further found that IgG-positive cells formed multiple layers around large ducts of pancreas from NOD mice. Our findings reveal the existence of periductal IgG-positive cells in the adult mouse pancreas, which were activated during streptozotocin-induced diabetes, adding a new dimension to our understanding of immunity in diabetes.
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PMID:IgG-positive cells surround pancreatic ducts and form multiple layers after streptozotocin treatment. 2400 Dec 4