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Endocrine Cells (endocrine + cell)
Selected AbstractsRole of adrenocorticotropic hormone in the development and maintenance of the adrenal cortical vasculatureMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2003Michaël Thomas Abstract The adrenal cortex is a highly vascularized endocrine tissue. A dense network of blood capillaries centripetally irrigates the adrenal gland, allowing every endocrine cell to be in contact with an endothelial cell. The pituitary hormone ACTH controls the coordinated development of the vasculature and the endocrine tissue mass. This suggests that paracrine secretions between steroidogenic adrenocytes and capillary endothelial cells participate in the control of adrenocortical homeostasis. Besides its effect on the vascular tone of arteries, ACTH induces the expression of the angiogenic cytokine VEGF-A (vascular endothelial growth factor-A) in primary cultures of adrenocortical cells. This growth factor is a specific mitogen for endothelial cells and is likely to mediate the hormonal control of adrenocortical vascularization through a paracrine mechanism. The newly discovered angiogenic factor EG-VEGF (endocrine-gland-derived vascular endothelial growth factor), the expression of which is restricted to endocrine glands and which is preferentially mitogenic for endocrine tissue-derived endothelial cells, is another candidate mediator of great potential interest. Microsc. Res. Tech. 61:247,251, 2003. © 2003 Wiley-Liss, Inc. [source] ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenumDEVELOPMENTAL DYNAMICS, Issue 1 2008Qian Wang Abstract Pax4 -deficient mice have a severe gastrointestinal endocrine deficiency: they lack most pancreatic cells that produce insulin or somatostatin and various duodenal endocrine cell types. Remarkably, Pax4 -deficient mice also have an overabundance of ghrelin-expressing cells in the pancreas and duodenum. Detailed analysis of the Pax4 nullizygous pancreas determined that the mutant islets are largely composed of a distinctive endocrine cell type that expresses ghrelin, glucagon, islet amyloid polypeptide (IAPP), and low levels of Pdx1. Lineage-tracing analysis revealed that most of these unique endocrine cells directly arose from Pax4 -deficient progenitors. Previous in vitro work reported that Pax4 is a transcriptional repressor of islet amyloid polypeptide (IAPP) and glucagon. In this study, we expanded those results by showing that Pax4 is also a repressor of gherlin. Together, our data further support the notion that Pax4 activity is necessary to establish appropriate patterns of gene expression in endocrine progenitors of the digestive tract. Developmental Dynamics 237:51,61, 2008. © 2007 Wiley-Liss, Inc. [source] Tissue surface tensions guide in vitro self-assembly of rodent pancreatic islet cellsDEVELOPMENTAL DYNAMICS, Issue 8 2007Dongxuan Jia Abstract The organization of endocrine cells in pancreatic islets is established through a series of morphogenetic events involving cell sorting, migration, and re-aggregation processes for which intercellular adhesion is thought to play a central role. In animals, these morphogenetic events result in an islet topology in which insulin-secreting cells form the core, while glucagon, somatostatin, and pancreatic polypeptide-secreting cells segregate to the periphery. Isolated pancreatic islet cells self-assemble in vitro into pseudoislets with the same cell type organization as native islets. It is widely held that differential adhesion between cells of the pancreatic islets generates this specific topology. However, this differential adhesion has never been rigorously quantified. In this manuscript, we use tissue surface tensiometry to measure the cohesivity of spherical aggregates from three immortalized mouse pancreatic islet cell lines. We show that, as predicted by the differential adhesion hypothesis, aggregates of the internally segregating INS-1 and MIN6 beta-cell lines are substantially more cohesive than those of the externally segregating ,-TC line. Furthermore, we show that forced overexpression of P-cadherin by ,-TC cells significantly perturbs the sorting process. Collectively, the data indicate that differential adhesion can drive the in vitro organization of immortalized rodent pancreatic islet cells. Developmental Dynamics 236:2039,2049, 2007. © 2007 Wiley-Liss, Inc. [source] Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signalingDEVELOPMENTAL DYNAMICS, Issue 4 2007Mamdouh H. Kedees Abstract Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the pancreatic epithelium is heterogeneous and comprised of subpopulations of exocrine/nestin-positive and endocrine/nestin-negative precursor cells. We examined this issue in two mutant mouse models characterized by protracted expression of several embryonal properties in islet cells. One mutant line comprises mice lacking mature glucagon due to abrogation of proprotein convertase-2 (PC2,/,), responsible for the conversion of proglucagon into glucagon, while the second line consists of mice with a global deletion of the glucagon receptor (Gcgr,/,). We demonstrate that nestin is transiently expressed by acinar cells and by insulin and glucagon cells of islets of both lines of mice. In addition, the lack of glucagon signaling increased nestin mRNA levels in pancreas of mutant embryos and adult mice. We conclude that nestin+ cells located in the pancreatic primordium generate the cells of the endocrine and exocrine lineages. Furthermore, our results suggest that nestin expression is regulated by glucagon signaling. Developmental Dynamics 236:1126,1133, 2007. © 2007 Wiley-Liss, Inc. [source] Analysis of pancreatic endocrine development in GDF11-deficient miceDEVELOPMENTAL DYNAMICS, Issue 11 2006Darwin S. Dichmann Abstract Here, we examine the role of GDF11 in pancreatic development. Using in situ hybridization and reverse transcriptase-polymerase chain reaction analyses, we show that Gdf11 transcripts are expressed in embryonic pancreas epithelium before the secondary transition but decrease rapidly afterward. To determine the function of GDF11 during pancreas development, we analyzed Gdf11,/, mouse embryos. In such embryos, pancreas size is twofold reduced at embryonic day (E) 18 compared with wild-type littermates. Quantification of the different tissue compartments shows a specific hypoplasia of the exocrine compartment, while the endocrine and ductal compartments are unaffected. Notably, NGN3+ endocrine precursor cells are increased fourfold at E18, although the amount of endocrine cells in the pancreas of these animals is unchanged compared with wild-type littermates. Similarly, the maturation of endocrine cells as well as the ratio between ,- and ,-cells appears normal. Developmental Dynamics 235:3016,3025, 2006. © 2006 Wiley-Liss, Inc. [source] ,-cell development: the role of intercellular signalsDIABETES OBESITY & METABOLISM, Issue 2008R. Scharfmann Understanding in detail how pancreatic endocrine cells develop is important for many reasons. From a scientific point of view, elucidation of such a complex process is a major challenge. From a more applied point of view, this may help us to better understand and treat specific forms of diabetes. Although a variety of therapeutic approaches are well validated, no cure for diabetes is available. Many arguments indicate that the development of new strategies to cure diabetic patients will require precise understanding of the way ,-cells form during development. This is obvious for a future cell therapy using ,-cells produced from embryonic stem cells. This also holds true for therapeutic approaches based on regenerative medicine. In this review, we summarize our current knowledge concerning pancreatic development and focus on the role of extracellular signals implicated in ,-cell development from pancreatic progenitors. [source] Structure and function studies of glucagon-like peptide-1 (GLP-1): the designing of a novel pharmacological agent for the treatment of diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2005Hongxiang Hui Abstract Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide secreted from gut endocrine cells in response to nutrient ingestion. The multifaceted actions of GLP-1 include the following: (1) the stimulation of insulin secretion and of its gene expression, (2) the inhibition of glucagon secretion, (3) the inhibition of food intake, (4) the proliferation and differentiation of beta cells, and (5) the protection of beta-cells from apoptosis. The therapeutic utility of the native GLP-1 molecule is limited by its rapid enzymatic degradation by a serine protease termed dipeptidyl peptidase-IV (DPP-IV). The present article reviews the research studies aimed at elucidating the biosynthesis, metabolism, and molecular characteristics of GLP-1 since it is from these studies that the development of a GLP-1-like pharmacological agent may be derived. Copyright © 2005 John Wiley & Sons, Ltd. [source] The role of pdx1 and HNF6 in proliferation and differentiation of endocrine precursorsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2004Laura Wilding Abstract Ex vivo expansion of embryonic stem cells (ES cells) or pancreatic stem cells for insulin delivery to diabetic patients provides potential for the restoration of islet function in these individuals. Understanding the spatial and temporal requirements of crucial factors for endocrine progenitor specification, proliferation, and terminal differentiation remains a major challenge in the field of pancreas development. Here, we provide speculation as to the role of pdx1 and HNF6 in these different stages of pancreatic endocrine cell development. At the time when islets begin to form within the pancreas, the expression patterns of pdx1 and HNF6 diverge, suggesting distinct functions for each of the genes over the course of endocrine cell development. The current body of evidence provides support for a role of both factors in early endocrine specification as well as a requirement for pdx1 in the generation of mature pancreatic endocrine cells. The precise temporal requirement of HNF6 in the production of terminally differentiated endocrine cells remains unclear. Future studies in this area will rely on conditionally manipulatable systems in combination with lineage-tracing studies for a more accurate assessment of pdx1 and HNF6 function at different stages along the pathway of endocrine cell development. Copyright © 2004 John Wiley & Sons, Ltd. [source] Specific dynamic and noninvasive labeling of pancreatic , cells in reporter miceGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 4 2005Ahmi Ben-Yehudah Abstract Noninvasive detection of differentiated cells is increasingly demanded for accurate and reliable assessments of both in vitro and in vivo experimental systems. Here we present an efficient, innovative approach for imaging the , cells of the pancreatic islets of Langerhans. The main physiologic function of , cells is glucose-stimulated insulin secretion. This function is facilitated through the synthesis and storage of insulin in secretory vesicles of , cells, which then release their contents when , cells are exposed to hyperglycemic conditions. To visualize , cells in vivo in the mouse, we used targeted mutagenesis techniques to construct a modified insulin II (InsII) gene allele, InsIIEGFP, that expresses a proinsulin-EGFP (enhanced green fluorescent protein) fusion peptide. The EGFP portion of this fusion is entirely within the C-peptide portion of the proinsulin peptide. This fusion protein is processed in , cells to insulin and EGFP-tagged C peptide, which are stored together in cytoplasmic secretory vesicles. The large amount of vesicular EGFP-tagged C peptide is evident as a characteristic robust and specific fluorescence pattern in the , cells of InsIIEGFP mice. This innovative method of visualizing , cells will be a useful tool in the study of both , cell physiology and the development of the endocrine cells of the pancreas.genesis 43:166,174, 2005. © 2005 Wiley-Liss, Inc. [source] The emerging role of adipocytokines as inflammatory mediators in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2005Konstantinos Karmiris MD Abstract Anorexia, malnutrition, altered body composition and development of mesenteric obesity are well known features of inflammatory bowel disease (IBD). Recent data suggest that dysregulation of protein secretion by white adipose tissue is involved in these manifestations of patients with IBD. Adipocytes are recently recognized as endocrine cells that secrete a variety of bioactive substances known as adipocytokines. There is evidence that adipocytokines are involved in inflammatory and metabolic pathways in human beings. Overexpression of adipocytokines such as leptin, adiponectin and resistin in mesenteric adipose tissue of operated patients with Crohn's disease has recently been reported, suggesting that mesenteric adipocytes in IBD may act as immunoregulating cells. Therefore, it could be suggested that adipocytokines play an important role in the disease pathogenesis. Moreover, modulators of mesenteric adipose function have been suggested as potential therapeutic drugs in IBD. In this review, the importance of white adipose tissue function and adipocytokines, is discussed with respect to IBD. [source] Human islet-derived precursor cells can cycle between epithelial clusters and mesenchymal phenotypesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Behrous Davani Abstract We showed previously that undifferentiated, proliferating human islet-derived precursor cells (hIPCs) are a type of mesenchymal stem/stromal cell (MSC) that can be induced by serum deprivation to form clusters and ultimately differentiate in vitro to endocrine cells. We also demonstrated that partially differentiated hIPC clusters, when implanted under the kidney capsules of mice, continued to differentiate in vivo into hormone-producing cells. However, we noted that not all hIPC preparations yielded insulin-secreting cells in vivo and that in some animals no hormone-expressing cells were found. This suggested that the implanted cells were not always irreversibly committed to further differentiation and may even de-differentiate to a mesenchymal phenotype. In this study, we show that human cells with a mesenchymal phenotype are indeed found in the grafts of mice implanted with hIPCs in epithelial cell clusters (ECCs), which are obtained after 4-day in vitro culture of hIPCs in serum-free medium (SFM); mesenchymal cells were predominant in some grafts. We could mimic the transition of ECCs to de-differentiated mesenchymal cells in vitro by exposure to foetal bovine serum (FBS) or mouse serums, and to a significantly lesser extent to human serum. In a complementary series of experiments, we show that mouse serum and FBS are more effective stimulants of mesenchymal hIPC migration than is human serum. We found that proliferation was not needed for the transition from ECCs to de-differentiated cells because mitomycin-treated hIPCs that could not proliferate underwent a similar transition. Lastly, we show that cells exhibiting a mesenchymal phenotype can be found in grafts of adult human islets in mice. We conclude that epithelial-to-mesenchymal transition (EMT) of cells in hIPC ECCs can occur following implantation in mice. This potential for EMT of human islets or differentiated precursor cells must be considered in strategies for cell replacement therapy for diabetes. [source] Embryonic gene expression and pro-protein processing of proSAAS during rodent developmentJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Daniel J. Morgan Abstract In vitro assays have demonstrated that peptides derived from the recently,identified proSAAS precursor inhibit prohormone convertase 1 (PC1) suggesting that this novel peptide may function as an endogenous inhibitor of PC1. To further understand the role of proSAAS in vivo, we have investigated the expression of proSAAS mRNA and processing of proSAAS during pre- and early postnatal rodent development. In situ hybridization showed that, by embryonic day 12.5 (e12.5) in the rat, proSAAS mRNA was present in essentially all differentiating neurons in the mantle layer of the myelencephalon, metencephalon, diencephalon, spinal cord and several sympathetic ganglia. During later stages of prenatal development, widespread proSAAS expression continues in post-mitotic neurons of both the CNS and PNS and begins in endocrine cells of the anterior and intermediate pituitary. Although proSAAS expression overlaps with PC1 in several regions, its overall expression pattern is significantly more extensive, suggesting that proSAAS may be multifunctional during development. Processed forms of proSAAS are present by at least mid-gestation with marked accumulation of two C-terminal forms, comprising the PC1 inhibitory fragment of proSAAS. [source] Increased synthesis but decreased processing of neuronal proCCK in prohormone convertase 2 and 7B2 knockout animalsJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Jens F. Rehfeld Abstract In addition to its role as a gut hormone, cholecystokinin (CCK) is a widespread and potent neurotransmitter. Its biosynthesis requires endoproteolytic cleavage of proCCK at several mono- and dibasic sites by subtilisin-like prohormone convertases (PCs). Of these, PC1 and PC2 are specific for neuroendocrine cells. We have now examined the role of PC2 and its binding protein, 7B2, in the neuronal processing of proCCK by measurement of precursor, processing-intermediates and bioactive end-products in brain extracts from PC2- and 7B2-null mice and from corresponding controls. PC2-null mice displayed a nine-fold increase of cerebral proCCK concentrations, and a two-fold increase in the concentrations of the processing-intermediate, glycine-extended CCK, whereas the concentrations of transmitter-active (i.e. ,-amidated and O -sulfated) CCK peptides were reduced (61%). Chromatography showed that O -sulfated CCK-8 still is the predominant transmitter-active CCK in PC2-null brains, but that the fraction of intermediate-sized CCK-peptides (CCK-58, -33 and -22) was eight-fold increased. 7B2-null brains displayed a similar pattern but with less pronounced precursor accumulation. In contrast with the cerebral changes, PC2 deficiency was without effect on proCCK synthesis and processing in intestinal endocrine cells, whereas 7B2 deficiency halved the concentration of bioactive CCK in the intestine. The results show that PC2 plays a major neuron-specific role in the processing of proCCK. [source] An Insight to Pituitary Folliculo-Stellate CellsJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2008S. Devnath Folliculo-stellate cells (FS-cells) are star-shaped and follicle-forming cells in the anterior pituitary gland that were first identified by electron microscopy as non-endocrine agranular cells. Light microscopy has revealed many of their cytophysiological features and the FS-cell is known to be positive for S-100 protein, a marker for FS-cells. So far, functions ascribed to FS-cells include the formation of an extensive and complex tridimentional network, scavenger activity by engulfing degenerated cells, paracrine regulation of endocrine cells by producing various growth factors and cytokines, such as interleukin-6, leukemia inhibitory factor, basic fibroblastic growth factor, vascular endothelial cell growth factor and follistatin, and large-scale inter-cellular communication by means of their long cytoplasmic processes and gap junctions. Moreover, their multi-potential characteristics and other cytological features support the possibility of them becoming organ-specific stem cells. This concept is yet to be resolved, however. In this review, we focus on these features of FS-cells along with some futuristic approaches. [source] Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion-affected expression, and impaired regenerative axonal growthJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2009Bettina A. Buhren Abstract Glucose-dependent insulinotropic polypeptide (GIP) was initially described to be rapidly regulated by endocrine cells in response to nutrient ingestion, with stimulatory effects on insulin synthesis and release. Previously, we demonstrated a significant up-regulation of GIP mRNA in the rat subiculum after fornix injury. To gain more insight into the lesion-induced expression of GIP and its receptor (GIPR), expression profiles of the mRNAs were studied after rat sciatic nerve crush injury in 1) affected lumbar dorsal root ganglia (DRG), 2) spinal cord segments, and 3) proximal and distal nerve fragments by means of quantitative RT-PCR. Our results clearly identified lesion-induced as well as tissue type-specific mRNA regulation of GIP and its receptor. Furthermore, comprehensive immunohistochemical stainings not only confirmed and exceeded the previous observation of neuronal GIP expression but also revealed corresponding GIPR expression, implying putative modulatory functions of GIP/GIPR signaling in adult neurons. In complement, we also observed expression of GIP and its receptor in myelinating Schwann cells and oligodendrocytes. Polarized localization of GIPR in the abaxonal Schwann cell membranes, plasma membrane-associated GIPR expression of satellite cells, and ependymal GIPR expression strongly suggests complex cell type-specific functions of GIP and GIPR in the adult nervous system that are presumably mediated by autocrine and paracrine interactions, respectively. Notably, in vivo analyses with GIPR-deficient mice suggest a critical role of GIP/GIPR signal transduction in promoting spontaneous recovery after nerve crush, insofar as traumatic injury of GIPR-deficient mouse sciatic nerve revealed impaired axonal regeneration compared with wild-type mice. © 2009 Wiley-Liss, Inc. [source] Recently identified a novel neuropeptide manserin colocalize with the TUNEL-positive cells in the top villi of the rat duodenumJOURNAL OF PEPTIDE SCIENCE, Issue 6 2008Aika Yajima Abstract We recently isolated a novel 40 amino acid neuropeptide designated manserin from the rat brain. Manserin is derived from secretogranin II, a member of granin acidic secretory protein family by proteolytic processing, as previously reported secretoneurin and EM66. Manserin peptide are localized in the endocrine cells of the pituitary. In this study, we further investigated the manserin localization in the digestive system by immunohistochemical analysis using antimanserin antibody. In the duodenum, manserin immunostaining was exclusively observed in the nuclei of top villi instead of cytosol as observed in neurons in our previous study. Interestingly, manserin-positive cells in the duodenum are colocalized with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive cells, the cells whose DNA was damaged. Since the top villi of duodenum epithelial cells are known to undergo spontaneous apoptosis during epithelial cell turn over, and since other peptides such as secretoneurin and EM66 derived from SgII have been reported to be cancer-related, these results indicated that manserin peptide may have a role in apoptosis and/or cancer pathogenesis in the digestive organ. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source] Dopamine modulates von Willebrand factor secretion in endothelial cells via D2,D4 receptorsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2006S. ZAREI Summary.,Objective: von Willebrand factor (VWF) is acutely released from endothelial cells in response to numerous calcium-raising agents (e.g. thrombin, histamine) and cAMP-raising agents (e.g. epinephrine, adenosine, vasopressin). In contrast, very few inhibitors of endothelial VWF secretion have been described. The neurotransmitter dopamine is a modulator of exocytosis in several endocrine cells, and is possibly involved in the regulation of several endothelial cell functions. We therefore investigated the effect of dopamine on endothelial VWF secretion. Results: Dopamine, D2/D3- and D4-specific agonists inhibited histamine- but not thrombin-induced VWF secretion. Expression of dopamine D2, D3 and D4 receptors was demonstrated by reverse transcription polymerase chain reaction (RT-PCR) in both human aortic (HAEC) and umbilical vein (HUVEC) endothelial cells. D2,D4 agonists did not inhibit histamine-induced rise in [Ca2+]i: they inhibited histamine-induced secretion even in the absence of extracellular calcium. Thus, the dopamine effects are not mediated by [Ca2+]i -dependent signalling. D2/D3- and D4-specific agonists inhibited neither the rise in cAMP nor VWF secretion in response to epinephrine and adenosine, arguing against an effect on cAMP-mediated signalling. D1 and D5 receptors were not detected in HAEC or HUVEC by RT-PCR, and the D1/D5-specific agonist SKF 38 393 failed to modulate VWF secretion, arguing against a role for these receptors in endothelial exocytosis. Conclusions: Dopamine inhibits histamine-induced endothelial exocytosis by activating D2,D4 receptor, via a mechanism distinct from [Ca2+]i -or cAMP-mediated signaling. In contrast, D1 and D5 receptors are not functionally expressed in cultured endothelial cells. Dopamine agonists may be useful as inhibitors of endothelial activation in inflammation and cardiovascular disease. [source] Changes of gastric mucosal architecture during long-term omeprazole therapy: results of a randomized clinical trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2006L. LUNDELL Summary Background, The impact of long-term acid suppression on the gastric mucosa remains controversial. Aim, To report further observations on an established cohort of patients with gastro-oesophageal reflux disease, after 7 years of follow-up. Methods, Of the original cohort randomized to either antireflux surgery or omeprazole, 117 and 98 patients remained in the medical and surgical arms, respectively. Gastric biopsies were taken at baseline and throughout the study. Results, Fifty-three antireflux surgery and 39 omeprazole-treated patients had Helicobacter pylori infection at randomization. Eighty-three omeprazole-treated and 60 antireflux surgery patients remained H. pylori negative over the 7 years, and no change was observed in mucosal morphology except for a change in endocrine cell population (linear and diffuse hyperplasia, P = 0.03). During the 7-year study many patients, who were initially H. pylori infected, had the infection eradicated leaving only 13 omeprazole and 12 antireflux surgery patients still infected. In these patients, omeprazole induced a deterioration of the mucosal inflammation scores (P = 0.01) with a numerical increase of glandular atrophy. Conclusions, Long-term omeprazole therapy does not alter the exocrine oxyntic mucosal morphology in H. pylori -negative patients, but mucosal endocrine cells appear to be under proliferative stimulation; in H. pylori -positive patients there are changes in mucosal inflammation and atrophy. [source] Review article: transcriptional events controlling the terminal differentiation of intestinal endocrine cellsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2000H. Mutoh Summary Secretin-producing enteroendocrine cells arise from a multipotential endocrine progenitor in the crypts of the small intestine. As these cells migrate up the crypt-villus axis, they produce secretin and stop dividing as they terminally differentiate and die. Transcription of the secretin gene is controlled by a complex enhancer binding to multiple transcription factors. The basic helix-loop-helix protein, BETA2, binds to an E box sequence and associates with the p300 coactivator to activate transcription of the secretin gene. Basic helix-loop-helix proteins appear to play a pivotal role in the control of cellular differentiation. BETA2 induces cell cycle arrest and apoptosis in addition to activating secretin gene expression. Thus BETA2 may function as a master regulatory gene to coordinate terminal differentiation of secretin cells. [source] Cells from bone marrow that evolve into oral tissues and their clinical applicationsORAL DISEASES, Issue 1 2007OM Maria There are two major well-characterized populations of post-natal (adult) stem cells in bone marrow: hematopoietic stem cells which give rise to blood cells of all lineages, and mesenchymal stem cells which give rise to osteoblasts, adipocytes, and fibroblasts. For the past 50 years, strict rules were taught governing developmental biology. However, recently, numerous studies have emerged from researchers in different fields suggesting the unthinkable , that stem cells isolated from a variety of organs are capable of ignoring their cell lineage boundaries and exhibiting more plasticity in their fates. Plasticity is defined as the ability of post-natal (tissue-specific adult) stem cells to differentiate into mature and functional cells of the same or of a different germ layer of origin. There are reports that bone marrow stem cells can evolve into cells of all dermal lineages, such as hepatocytes, skeletal myocytes, cardiomyocytes, neural, endothelial, epithelial, and even endocrine cells. These findings promise significant therapeutic implications for regenerative medicine. This article will review recent reports of bone marrow cells that have the ability to evolve or differentiate into oral and craniofacial tissues, such as the periodontal ligament, alveolar bone, condyle, tooth, bone around dental and facial implants, and oral mucosa. [source] Non-cystic solid-pseudopapillary tumor of the pancreas showing nuclear accumulation and activating gene mutation of ,-cateninPATHOLOGY INTERNATIONAL, Issue 11 2006Isao Nishimori Solid-pseudopapillary tumor (SPT) is an unusual pancreatic neoplasm that is characterized by a mixture of solid and cystic components and a fibrous capsule. Recently, the tumorigenesis of SPT has been reported to be associated with gene mutations of ,-catenin, which is a molecule participating in the Wnt signaling pathway. Reported herein is the case of a 53-year-old woman with SPT. The tumor, approximately 3 cm in diameter in the pancreas body, had a clear margin and central calcification but had neither a cystic component nor fibrous capsule. Several lines of pathological findings in the surgically resected specimen indicated SPT: (i) pseudopapillary proliferation of eosinophilic polygonal cells with oval nuclei; (ii) positive expression of several marker molecules indicating differentiation into acinar and endocrine cells; and (iii) zymogen granule-like structures in the cytoplasm on electron microscopy. Further, the tumor cells had intense nuclear accumulation of ,-catenin and an activating mutation, 34Gly(GGA) to Arg(AGA), in exon 3 of the ,-catenin gene, as previously reported in most SPT. These findings suggest that association of the ,-catenin phenotype with development of the rare phenotype of SPT, a non-cystic and unencapsulated tumor, is unlikely. [source] Coexistence of gastric- and intestinal-type endocrine cells in gastric and intestinal mixed intestinal metaplasia of the human stomachPATHOLOGY INTERNATIONAL, Issue 4 2005Takafumi Otsuka Intestinal metaplasia (IM) in the human stomach has previously been classified into a gastric and intestinal mixed (GI-IM) and a solely intestinal phenotype (I-IM). The phenotypes of mucous and endocrine cells were evaluated in 3034 glandular ducts associated with chronic gastritis. In the pyloric region, the relative expression of gastric endocrine cell markers, such as gastrin and somatostatin, decreased gradually from glandular ducts with only gastric mucous cell phenotype (G type) to GI-IM toward I-IM, while that of the intestinal endocrine cell markers, glicentin, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) was inversely correlated. In the fundic region, gastrin-positive, cells, emerged, in, the, pseudo-pyloric, and, GI-IM glands, whereas I-IM glands did not possess any gastrin-positive cells, suggesting the presence of a distinct pathway of intestinalization. Double staining revealed coexistence of gastrin- and GLP-1-positive cells in the same gland and occasionally in the same cell in GI-IM glands. These results suggest that the phenotypes of endocrine cells are in line with those for mucous counterparts and support the concept that all of the different types of mucous and endocrine cells in normal and IM glands might be derived from a single progenitor cell in each gland. [source] ,-Latrotoxin increases spontaneous and depolarization-evoked exocytosis from pancreatic islet ,-cellsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Amelia M. Silva ,-Latrotoxin (,-LT), a potent excitatory neurotoxin, increases spontaneous, as well as action potential-evoked, quantal release at nerve terminals and increases hormone release from excitable endocrine cells. We have investigated the effects of ,-LT on single human, mouse and canine ,-cells. In isolated and combined measurements, ,-LT, at nanomolar concentrations, induces: (i) rises in cytosolic Ca2+, into the micromolar range, that are dependent on extracellular Ca2+; (ii) large conductance non-selective cation channels; and (iii) Ca2+ -dependent insulin granule exocytosis, measured as increases in membrane capacitance and quantal release of preloaded serotonin. Furthermore, at picomolar concentrations, ,-LT potentiates depolarization-induced exocytosis often without evidence of inducing channel activity or increasing cytosolic Ca2+. These results strongly support the hypothesis that ,-LT, after binding to specific receptors, has at least two complementary modes of action on excitable cells. (i) ,-LT inserts into the plasma membrane to form Ca2+ permeable channels and promote Ca2+ entry thereby triggering Ca2+ -dependent exocytosis in unstimulated cells. (ii) At lower concentrations, where its channel forming activity is hardly evident, ,-LT augments depolarization-evoked exocytosis probably by second messenger-induced enhancement of the efficiency of the vesicle recruitment or vesicle fusion machinery. We suggest that both modes of action enhance exocytosis from a newly described highly Ca2+ -sensitive pool of insulin granules activated by global cytosolic Ca2+ concentrations in the range of ,1 ,m. [source] Lymphatic Vessels in Pancreatic Islets Implanted Under the Renal Capsule of RatsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2006Ö. Källskog Transplantation of pancreatic islets necessitates an engraftment process, including revascularization of the graft. Studies of graft vasculature have demonstrated that islets become revascularized during the first post-transplant week through an angiogenic process. If this also involves lymphatic vessels is unknown. The aim of the present study was to functionally evaluate if lymphatic vessels, which are absent in endogenous islets, form after islet transplantation. To achieve this, inbred Wistar-Furth rats were transplanted with 250 syngeneic islets under the renal capsule. Intra-vital microscopy of the graft in combination with interstitial injection of Evans Blue was performed 1 week, 1 month or 9,12 months later. In all animals studied, there was drainage through intra-graft lymphatic capillaries emptying into larger lymphatic vessels associated with the renal capsule. The number was slightly lower 1 week post-transplantation. Most of the lymphatic capillaries were present in the graft stroma, rather than interspersed among the endocrine cells. In some animals, we were able to demonstrate dye in regional lymph nodes. We conclude that unlike endogenous islets, islet grafts develop a lymphatic drainage. Its functional importance and characteristics remain to be established. However, it can be speculated that immune reactions may be facilitated by the presence of lymphatic vessels. [source] Immunodetection of Cocaine- and Amphetamine-Regulated Transcript in the Rumen, Reticulum, Omasum and Abomasum of the SheepANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2009M. B. Arciszewski Summary Enteric nerves harbour a wide array of neuropeptides playing a key role in the regulation of gastrointestinal tract functions. In this study, the distribution patterns of cocaine- and amphetamine-regulated transcript-immunoreactive (CART-IR) nerve fibres as well as the percentages of CART-positive enteric neurons were immunohistochemically assessed in the rumen, reticulum, omasum and abomasum of the sheep. Double staining were applied, to elucidate whether neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), somatostatin or serotonin co-exist in CART-IR gastric structures. In the rumen, reticulum, omasum and abomasum, a majority of myenteric neurons identified by immunoreactivity to Hu C/D were CART-positive (47.1 ± 3.6%, 45.1 ± 3.0%, 41.6 ± 2.6% and 40.9 ± 2.9% respectively). The smooth musculature of the forestomachs as well as abomasum was innervated with numerous CART-IR nerve fibres. Blood vessels-associated CART-positive nerve terminals were identified in the submucosa of the reticulum only. Lamina muscularis mucosae of the omasum and abomasum was moderately innervated with CART-IR nerve terminals. In the abomasum sparse CART-IR nerve fibres were seen between mucosal glands. A small population of endocrine cells of the abomasum also exhibited the presence of CART. All neuronal elements as well as endocrine cells IR to CART were negative to somatostatin and/or serotonin. No immunoreactivity to VIP, NPY and/or SP was found in myenteric ganglia-projecting CART-positive nerve fibres. The co-localization of CART with VIP, NPY and/or SP was regularly observed in myenteric neurons as well as the smooth muscle layer- and lamina muscularis mucosae-projecting nerve fibres. CART-IR nerve terminals located between mucosal glands of the abomasum frequently co-stored VIP, NPY and/or SP. Although the exact function of CART in the ovine forestomachs/stomach has to be elucidated, several potential functions (like enteric nerves protection) have been suggested. [source] Serum ghrelin concentrations in patients with chronic renal failure undergoing dialysisCLINICAL ENDOCRINOLOGY, Issue 1 2006Pedro Iglesias Summary Background, ,Ghrelin is a recently discovered protein hormone mainly synthesized in the gastric endocrine cells. This hormone not only is a potent growth hormone secretagogue but also is involved in the regulation of food ingestion and energy metabolism. Derangements in ghrelin secretion in patients with chronic renal failure (CRF) have not been fully evaluated. Objective, ,Our aim has been to quantify serum concentrations of total ghrelin in a group of patients with CRF on chronic therapy with both haemodialysis (HD) and peritoneal dialysis (PD) in comparison with a group of patients on conservative management (predialysis). Patients and measurements, ,We studied 68 CRF patients treated by HD (n = 30, 16 men, age 61·2 ± 1·8 years) and PD groups (n = 38, 21 men, age 54·4 ± 1·7 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of ghrelin, leptin, insulin, IGF I and GH were measured in all subjects. Results, ,Patients undergoing HD showed similar concentrations of ghrelin in comparison with the control group (9491 ± 787 vs 9280 ± 918 pg/ml, NS). However, PD patients exhibited baseline ghrelin concentrations significantly lower than those found in patients on conservative management (3230 ± 216 pg/ml, P < 0·0001). Men and women showed similar serum ghrelin levels in both HD (9845·9 ± 1071 vs 9085 ± 1194 pg/ml) and PD patients (3214 ± 297 vs 3250 ± 324 pg/ml). Hypertension and diabetes mellitus did not influence ghrelin levels. Serum GH levels were positively correlated with serum ghrelin concentrations in both HD (r = 0·46, P < 0·05) and PD (r = 0·53, P < 0·001) patients; however, no relationships between ghrelin, leptin, insulin and IGF I were found. Conclusions, ,These results suggest that PD is accompanied by a striking decrement in baseline ghrelin concentrations in comparison with values found both in HD and control patients. Further studies are necessary to determine mechanisms involved in ghrelin regulation in uraemic patients. [source] Analysis of cell signalling in the rodent pineal gland deciphers regulators of dynamic transcription in neural/endocrine cells,EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001Jörg H. Stehle Abstract In neurons, a temporally restricted expression of cAMP-inducible genes is part of many developmental and adaptive processes. To understand such dynamics, the neuroendocrine rodent pineal gland provides an excellent model system as it has a clearly defined input, the neurotransmitter norepinephrine, and a measurable output, the hormone melatonin. In this system, a regulatory scenario has been deciphered, wherein cAMP-inducible genes are rapidly activated via the transcription factor phosphoCREB to induce transcriptional events necessary for an increase in hormone synthesis. However, among the activated genes is also the inhibitory transcription factor ICER. The increasing amount in ICER protein leads ultimately to the termination of mRNA accumulation of cAMP-inducible genes, including the gene for the Aa-nat that controls melatonin production. This shift in ratio of phosphoCREB and ICER levels that depends on the duration of stimulation can be interpreted as a self-restriction of cellular responses in neurons and has also been demonstrated to interfere with cellular plasticity in many non-neuronal systems. [source] | |||||||||||||