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)

During migration and for about 2 days after their arrival in the gonadal ridges, primordial germ cells (the embryonic precursors of gametes of the adult animal) proliferate actively. Certain growth factors, such as stem cell factor and leukemia inhibitory factor, seem to be essential for survival, proliferation and possibly differentiation of mouse primordial germ cell in vivo and/or in vitro. Similarly, increase in intracellular cAMP is followed by a marked enhancement of primordial germ cell proliferation, at least in culture. In the present study, we show that pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38), two neuropeptides of the secretin-glucagon-vasoactive intestinal polypeptide-GH-releasing hormone family, stimulate in vitro proliferation of mouse primordial germ cells, bind to primordial germ cells and gonadal somatic cells (possibly to type I PACAP receptor) and activate adenylate cyclase in the same cells. Moreover, PACAP-like immunoreactivity was found in gonadal ridges, mostly on germ cell surface. In conclusion, evidence is provided that PGC proliferation can be stimulated by certain bioactive polypeptides, thus suggesting a novel regulatory role for such compounds in early gonad development.
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PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates adenylate cyclase and promotes proliferation of mouse primordial germ cells. 856 32

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

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

Growth hormone-releasing hormone (GHRH) belongs to a family of peptides expressed at high levels in the brain and digestive system of mammals. We have identified GHRH mRNA and peptide in rat and human germ cells, and detected a GHRH receptor mRNA in Sertoli cells. GHRH treatment of cultured Sertoli cells results in accumulation of cAMP and increased expression ofc-fos and stem cell factor (SCF), two factors critical for normal germ cell development. The current study was designed to localize within testis the transcription of other members of the GHRH family, and their receptors, and to determine if they also stimulate SCF. RNAs from separated testicular cells were amplified by comparative reverse transcription-polymerase chain reaction (RT-PCR). Southern blot analysis of the PCR products verified the presence of five GHRH family peptide and receptor transcripts in distinct testicular cell types. Transcripts encoding VIP and glucagon, and the receptors for pituitary adenylate cyclase activating peptide (PACAP) and glucagon, were detected predominantly in Leydig cells. In contrast, expression of GHRH, PACAP, secretin, and secretin receptor predominated in germ cells. Receptors for GHRH and VIP were expressed equally in all testicular cell types. To determine if, like GHRH, any of these other peptides activate Sertoli cell expression of SCF, primary Sertoli cell cultures were treated for 4-6 h with 10 or 100 nM of each individual factor. There was no consistent stimulation of SCF mRNA by VIP, PACAP, glucagon, or secretin. Differential expression of these peptides and their receptors suggests that they may each have unique paracrine functions within the testis.
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PMID:Peptides of the growth hormone-releasing hormone family : Differential expression in rat testis. 2115 94