Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory ...
Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory ...
This study examined whether the densities of stem- and enteroendocrine cell progenitors are abnormal in the ileum of patients with irritable bowel syndrome (IBS), and whether any abnormalities in ileal enteroendocrine cells are correlated with abnormalities in stem cells and enteroendocrine cell progenitors. One hundred and one IBS patients covering all IBS subtypes were recruited, and 39 non-IBS subjects were included as a control group. The patients and controls underwent standard colonoscopies, during which biopsy specimens were obtained from the ileum. The biopsy specimens were stained with hematoxylin-eosin and immunostained for Musashi-1 (Msi-1), neurogenin 3 (NEUROG3), chromogranin A (CgA), serotonin, peptide YY (PYY), oxyntomodulin (enteroglucagon), pancreatic polypeptide, and somatostatin. The immunoreactive cells were quantified by computerized image analysis. The densities of Msi-1, NEUROG3, CgA, and serotonin cells were reduced in all IBS patients and in patients with diarrhea-predominant
The endocrine system employs peptide hormone signals to translate environmental changes into physiological responses. The diffuse endocrine system embedded in the gastrointestinal barrier epithelium is one of the largest and most diverse endocrine tissues. Furthermore, it is the only endocrine tissue in direct physical contact with the microbial environment of the gut lumen. However, it remains unclear how this sensory epithelium responds to specific pathogenic challenges in a dynamic and regulated manner. We demonstrate that the enteroendocrine cells of the adult Drosophila melanogaster midgut display a transient, sensitive, and systemic induction of the pro-secretory factor dimmed (dimm) in response to the Gram-negative pathogen Pseudomonas entomophila (Pe). In enteroendocrine cells, dimm controls the levels of the targets Phm, dcat-4 and the peptide hormone, Allatostatin A. Finally, we identify dimm as a host factor that protects against Pe infection and controls the expression of ...
TY - JOUR. T1 - Coexistence of gastric- and intestinal-type endocrine cells in gastric and intestinal mixed intestinal metaplasia of the human stomach. AU - Otsuka, Takafumi. AU - Tsukamoto, Tetsuya. AU - Mizoshita, Tsutomu. AU - Inada, Ken Ichi. AU - Takenaka, Yoshiharu. AU - Kato, Sosuke. AU - Yamamura, Yoshitaka. AU - Miki, Kazumasa. AU - Tatematsu, Masae. PY - 2005/4/1. Y1 - 2005/4/1. N2 - 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), ...
Glutamine-evoked cAMPi responses in GLUTag cells. GLUTag cells were transfected with the cAMP probe, Epac2 camps. FRET was measured as the YFP/CFP ratio by exci
J:112173 Gierl MS, Karoulias N, Wende H, Strehle M, Birchmeier C, The Zinc-finger factor Insm1 (IA-1) is essential for the development of pancreatic beta cells and intestinal endocrine cells. Genes Dev. 2006 Sep 1;20(17):2465-78 ...
Billing JL, Larraufie P, Lewis J, Leiter A, Li J, Lam B, Yeo GSH, Goldspink DA, Kay RG, Gribble FM, Reimann F. Single cell transcriptomic profiling of large intestinal enteroendocrine cells in mice - identification of selective stimuli for Insulin-like peptide-5 and Glucagon-like peptide-1 co-expressing cells. Mol Metab. 2019 Nov;29:158-169. PMID: 31668387. PMCID: PMC6812004. Adriaenssens AE, Biggs EK, Darwish T, Tadross J, Sukthankar T, Girish M, Polex-Wolf J, Lam BY, Zvetkova I, Pan W, Chiarugi D, Yeo GSH, Blouet C, Gribble FM, Reimann F. Glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake. Cell Metab. 30(5):987-996 PMID:31447324, PMCID: PMC6838660. Lu VB, Rievaj J, OFlaherty EA, Smith CA, Pais R, Pattison LA, Tolhurst G, Leiter AB, Bulmer DC, Gribble FM, Reimann F. Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons. Nat Commun. 2019 Mar 4;10(1):1029. doi: ...
Intestinal hormones are key regulators of digestion and energy homeostasis secreted by rare enteroendocrine cells. These cells produce over ten different hormones including GLP-1 and GIP peptides known to promote insulin secretion. To date, the molecular mechanisms controlling the specification of the various enteroendocrine subtypes from multipotent Neurog3+ endocrine progenitor cells, as well as their number, remain largely unknown. In contrast, in the embryonic pancreas, the opposite activities of Arx and Pax4 homeodomain transcription factors promote islet progenitor cells towards the different endocrine cell fates. In this study, we thus investigated the role of Arx and Pax4 in enteroendocrine subtype specification. The small intestine and colon of Arx- and Pax4-deficient mice were analyzed using histological, molecular, and lineage tracing approaches. We show that Arx is expressed in endocrine progenitors (Neurog3+) and in early differentiating (ChromograninA−) GLP-1-, GIP-, CCK-, Sct- Gastrin-
In this project from scientists at Stanford University School of Medicine and other institutions, comparative RNA-seq was used to analyze putative mouse intestinal stem cells. The teams findings have implications for cellular plasticity and better understanding stem cells in general. Pippin Prep was used to size libraries before sequencing.. Citation: ...
Fingerprint Dive into the research topics of Pharmacological potential of novel agonists for FFAR4 on islet and enteroendocrine cell function and glucose homeostasis. Together they form a unique fingerprint. ...
Enteroendocrine cell definition at Dictionary.com, a free online dictionary with pronunciation, synonyms and translation. Look it up now!
Has established three new collaborations with investigators at other institutions. Major Accomplishments:. Since starting the Pathway award in 2016, my laboratory has: (1) defined the microRNA landscape in several functionally-distinct cell types of the small intestinal epithelium, (2) determined the sensitivity of microRNAs in these cell types to gut microbes and high-fat diet (HFD), and (3) identified specific microRNAs that may play an important role in intestinal stem cell (ISC) homeostasis, which is critical for proper intestinal physiology and metabolic balance.. Our work shows that only a handful of microRNAs are significantly altered by the presence of gut microbes or by HFD in small intestinal enteroendocrine cells (EEC), which are critical for metabolic balance. Based on known functions of some of these microRNAs in pancreatic beta cells, we hypothesize that they may regulate the secretion of gut hormones from EECs. We also determined that microRNAs in ISCs are by far the most ...
Rashmi Chandra,1 Annie Hiniker,2 Yien-Ming Kuo,3 Robert L. Nussbaum,3,4 and Rodger A. Liddle1,5 First published June 15, 2017 - More info Abstract Parkinsons disease (PD) is a progressive neurodegenerative disease with devastating clinical manifestations. In PD, neuronal death is associated with intracellular aggregates of the neuronal protein α-synuclein known as Lewy bodies. Although the cause…
Principal Investigator:FUJIMIYA Mineko, Project Period (FY):2001 - 2002, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:General anatomy (including Histology/Embryology)
This is the first report of the immunohistological features of resolution of acute Campylobacterenterocolitis, and the first to report the striking increase in EC numbers and changes in macrophages and T lymphocytes which, in at least some patients, can persist for more than a year. This description is particularly important because similar changes were found in outpatients with prolonged IBS symptoms following acute bacterial enteritis. The persistence of these changes and their detection in symptomatic outpatients supports our hypothesis that the changes we have described following bacterial enteritis are in part responsible for the persistent symptoms commonly seen in clinical practice. This cohort study required a rather arduous protocol, with patients undergoing three rectal biopsies and two determinations of gut permeability. Although 47 patients agreed to participate, only 21 completed the three visits. However, as shown in table 1, those who did were demographically similar to those who ...
Our results demonstrate a direct link between SCFA activation of FFAR2, elevation of intracellular Ca2+ in L cells, and enhanced GLP-1 secretion from primary colonic cultures. A stimulatory role for FFAR2 in vivo is supported by the finding that knockout of ffar2 lowers both basal and glucose-stimulated GLP-1 concentrations.. By quantitative PCR, we could demonstrate that expression of mRNA for ffar2 and ffar3 is enriched in L cells, consistent with the detection of these receptors in PYY- and GLP-1-positive cells in rat and human colon by immunohistochemistry (21-23). Interestingly, ffar2 expression was very low in the GLP-1-secreting cell line GLUTag, perhaps explaining the poor responsiveness of GLUTag cells to SCFAs (data not shown) and emphasizing the importance of studying primary L cells in parallel with cell line models.. FFAR2 reportedly couples to Gq- or Gi/o-signaling pathways and FFAR3 exclusively to Gi. The finding that GLP-1 secretion is enhanced, rather than inhibited, by SCFAs ...
We found that WNT/FGF require BMP activity to initiate posterior gene expression, consistent with the known role of BMP as a posteriorizing factor11C13. antral mucous cells, and a diversity of gastric endocrine cells. We used hGO cultures to identify novel signaling mechanisms that regulate early endoderm patterning and gastric endocrine cell differentiation upstream of the transcription factor NEUROG3. Using hGOs to model pathogenesis of human disease, we found that infection resulted in rapid association of the virulence factor CagA with the c-Met receptor, activation of signaling and induction of epithelial proliferation. Together, these studies describe a novel and robust system for elucidating AN7973 the mechanisms underlying human stomach development and disease. is then patterned along the anterior-to-posterior (ACP) axis and transformed into a gut tube consisting of Sox2+ foregut in the anterior and Cdx2+ mid-hindgut in the posterior (Fig. 1a). We previously demonstrated that WNT3A and ...
The hexokinase GK (glucokinase) plays a critical role in the regulation of hepatic glucose metabolism [1-4]. It has a relatively low affinity for glucose (approximately 7.5 mM), allowing it to adjust its activity precisely in response to physiological changes in blood and intrahepatic glucose concentrations. This enables effective clearance of glucose from the blood after a meal. In contrast with other hexokinases, GK displays a sigmoidal activity curve with regard to glucose and is not inhibited by its product, glucose 6-phosphate, or other metabolites [4,5]. Approximately 99.9% of the bodys entire supply of GK resides in the liver, with the remainder expressed in the endocrine cells of the pancreas, enteroendocrine cells, pituitary gonadotropes and selected nuclei of the central nervous system [3].. Gene expression and post-translational regulation of GK are profoundly influenced by its location in the body. In the liver its expression is effectively controlled by insulin such that absence of ...
See all of Dr. Leturques videos here]. The intestine provides an interface with environmental factors, transferring nutrients to the organism, while maintaining an efficient barrier against toxins and bacteria. Intestine has gained new attention for its roles in metabolic diseases. Effective treatments for reduction of obesity are bariatric surgeries that are often followed by increased gut-hormone secretion. Gut-hormone therapies (GLP-1 analogue and DPPIV inhibitors) are developed to treat type2 diabetic patients. A controversy on the stabilized GLP-1 analogues emerged due to cases of pancreatitis sometimes leading to cancer. There is thus an urge to find strategies to stimulate endogenous GLP-1 secretion by obese and diabetic subjects by a better knowledge of enteroendocrine cell lineage and functions. Furthermore, changes in gut microbiota are reported in metabolic diseases. However, the role of epithelial gut barrier between microbiota and related inflammation remains to be characterized in ...
Previously, we showed that receptor for activated C kinase 1 (Rack1) regulates growth of colon cells in vitro, partly by suppressing Src kinase activity at key cell cycle checkpoints, in apoptotic and cell survival pathways and at cell-cell adhesions. Here, we generated mouse models of Rack1 deficiency to assess Rack1s function in intestinal epithelia in vivo. Intestinal Rack1 deficiency resulted in proliferation of crypt cells, diminished differentiation of crypt cells into enterocyte, goblet, and enteroendocrine cell lineages, and expansion of Paneth cell populations. Following radiation injury, the morphology of Rack1-deleted small bowel was strikingly abnormal with development of large polypoid structures that contained many partly formed villi, numerous back-to-back elongated and regenerating crypts, and high-grade dysplasia in surface epithelia. These abnormalities were not observed in Rack1-expressing areas of intestine or in control mice. Following irradiation, apoptosis of enterocytes ...
PubMed] [Google Scholar] 14. the intestine, termed enteroids, has provided new possibilities for culturing M cells. Enteroids are advantageous over standard cultured cell lines because they can be differentiated into several major cell types found in the intestine, including goblet cells, Paneth cells, enteroendocrine cells and enterocytes. The cytokine RANKL LY2922470 is essential in M cell development, and addition of RANKL and TNF- to culture media promotes a subset of cells from ileal enteroids to differentiate into M cells. The following protocol describes a method for the differentiation of M cells in a transwell epithelial polarized monolayer system of the intestine using human ileal enteroids. This method can be applied to the study of M cell development and function. and 4 C for 5 min. Pellet should be visible but can easily be dislodged, so slowly remove the supernatant by vacuum aspiration or with a pipette.NOTE: If concerned LY2922470 about loss of pellet and cells, use a pipette and ...
The basal portion (further from lumen) of an intestinal crypt. Contains multipotent stem cells. Stem cells in the crypts divide to form daughter cells. One daughter cell from each stem cell division is retained as a stem cell. The other becomes committed to differentiate along one of four pathways to become an enterocyte, enteroendocrine cell, goblet cell or Paneth cell. [ http://orcid.org/0000-0002-6601-2165 ...
The mucosa is referred to as a mucous membrane, because mucus production is a characteristic feature of gut epithelium. The membrane consists of epithelium, which is in direct contact with ingested food, and the lamina propria, a layer of connective tissue analogous to the dermis. In addition, the mucosa has a thin, smooth muscle layer, called the muscularis mucosa (not to be confused with the muscularis layer, described below).. Epithelium-In the mouth, pharynx, oesophagus, and anal canal, the epithelium is primarily a non-keratinised, stratified squamous epithelium. In the stomach and intestines, it is a simple columnar epithelium. Notice that the epithelium is in direct contact with the lumen, the space inside the gastrointestinal tract. Interspersed among its epithelial cells are goblet cells, which secrete mucus and fluid into the lumen, and enteroendocrine cells, which secrete hormones into the interstitial spaces between cells. Epithelial cells have a very brief lifespan, averaging from ...
The mucosa is referred to as a mucous membrane, because mucus production is a characteristic feature of gut epithelium. The membrane consists of epithelium, which is in direct contact with ingested food, and the lamina propria, a layer of connective tissue analogous to the dermis. In addition, the mucosa has a thin, smooth muscle layer, called the muscularis mucosa (not to be confused with the muscularis layer, described below).. Epithelium-In the mouth, pharynx, esophagus, and anal canal, the epithelium is primarily a non-keratinized, stratified squamous epithelium. In the stomach and intestines, it is a simple columnar epithelium. Notice that the epithelium is in direct contact with the lumen, the space inside the alimentary canal. Interspersed among its epithelial cells are goblet cells, which secrete mucus and fluid into the lumen, and enteroendocrine cells, which secrete hormones into the interstitial spaces between cells. Epithelial cells have a very brief lifespan, averaging from only a ...
amino acids, polyamines, basic polypeptides, gamma glutamyl peptides, and other peptides, also activate CaSR in an allosteric manner. Its broad ligands and wide expression profile suggest multiple functions of CaSR in different tissues. This chapter reviews the functions of CaSR in the gastrointestinal tract. Specifically, a role for CaSR in luminal nutrient sensing in the enteroendocrine system is described.. ...
Scanty argyrophil cells are present in a substantial proportion of normal endometria, particularly during the secretory stage of the cycle. Argyrophil cells are also present in the various types of hyperplastic endometria and are found in more than half of endometrial adenocarcinomas. In some endometrial neoplasms they are present in abundance, but tumours rich in such cells do not have any features suggestive of a carcinoid tumour and are morphologically identical to adenocarcinomas of similar grade which are devoid of argyrophil cells. Endometrial adenocarcinomas containing argyrophil cells tend to be well differentiated and tend not to invade deeply into the myometrium. It is suggested that Müllerian epithelial stem cells possess a potentiality for differentiation into APUD cells.. ...
Argentaffin refers to cells which take up silver stain.[1] Enteroendocrine cells are sometimes also called argentaffins, because they take up this stain. An argentaffin cell is any enteroendocrine cell, a hormone-secreting cell present throughout the digestive tract. It is a property of melanin, and special stain can be applied to identify those granules. Fontana-Masson stain uses the fact that those cells can reduce the silver salts to metallic silver (brownish-black) color without the aid of reducing agent, which is the definition of Argentaffin cells. Argentaffin cell, one of the round or partly flattened cells occurring in the lining tissue of the digestive tract and containing granules thought to be of secretory function. These epithelial cells, though common throughout the digestive tract, are most concentrated in the small intestine and appendix. The cells located randomly within the mucous membrane lining of the intestine and in tubelike depressions in that lining known as the ...
Dr. Nakakuras laboratory has a long-term interest to elucidate the transcriptional and signaling events critical to the pathogenesis of NETs of the small intestine and pancreas, which can identify novel targets for diagnosis and treatment. His approach has been to turn to developmental biology for clues. Dr. Nakakura and collegues have found that the same transcription factors (Ascl1, Nkx2.2, Fev, Scratch)1-4 and signaling pathways (Notch)2 that function in the normal development of endocrine cells throughout the body also act to regulate NET hormone production and growth, as well as metastasis. These findings that conserved pathways of neuroendocrine differentiation function in cancer have also shed important insight into normal gut endocrine cell development. 1 Nakakura EK, Watkins DN, Schuebel KE, Sriuranpong V, Borges MW, Nelkin BD, Ball DW. Mammalian Scratch: a neural-specific Snail family transcriptional repressor. Proc Natl Acad Sci U S A, Mar/27/2001;98(7):4010-5. PMID: 11274425 2 ...
With its stem cells, the intestine is able to regenerate itself continuously and to ensure the function and integrity of the tissue during the lifespan of an organism, says Dr. Jerome Korzelius, first author of the study published in Nature Communications.. Asymmetric cell division of intestinal stem cells. Asymmetric division of ISCs is crucial for the process of cell renewal. An ISC renews by dividing into another stem cell and an enteroblast (EB) daughter cell. This daughter cell can then differentiate into two different types of differentiated cells depending on signaling cues: absorptive enterocytes (EC), cells that take up nutrients and are responsible for immune defense or enteroendocrine cells (EE) that produce gastrointestinal hormones. Recent work has shown that lineage choice in these EB daughter cells is likely more complex than previously thought.. Transcription factor Klumpfuss as regulator. The researchers discovered that the transcription factor Klumpfuss (Klu), which is related ...
The results of these experiments contrast with prior (similarly powered) reports that TCF7L2 and WFS1 alter β-cell responsiveness to infused GLP-1 and that variants in KCNQ1 alter GLP-1 concentrations after an oral challenge in nondiabetic humans. While far from conclusive, these results highlight the importance of independent replication prior to concluding that a given genotype has a particular effect on a complex phenotype.. Although TCF7L2 regulates proglucagon expression in enteroendocrine cells, diabetes-associated variation in this locus has not been previously associated with a defective rise in GLP-1 concentrations after oral challenge (18). In the same study, 81 healthy male subjects with the diabetes-associated allele of TCF7L2 (at rs7903146) had an impaired insulin secretory response to infused GLP-1 and decreased glucagon secretion during a 24 h period (18). Although this is congruent with the Schäfer et al. (8) study, it differs from our observation that after adjusting for age ...
My research interest is studying the roles of epigenetic genes that control gut neuromuscular disorders. The gut is a vital organ as it is where food is digested, where nutrients are absorbed into the bloodstream, and where undigested waste moves through and leaves the body. This digestive process is achieved by the synchronized movement (motility) of gastrointestinal (GI) muscles, which mixes food and propels the digested content through the GI tract.. Several cell types control GI motility: enteric nervous system (ENS), interstitial cells of Cajal (ICC), PDGFRα+ cells (fibroblast-like cells), and smooth muscle cells (SMC). ICC generates spontaneous electrical slow waves, ENS produces complex rhythmic motor behavior, and PDGFRα+ cells mediate enteric inhibitory responses, all of which control SMC, the final effectors for muscle contraction and muscle relaxation. In addition, enteroendocrine cells such as enterochromaffin (EC) cells secreting serotonin produce GI hormones or peptides that ...
The gastrointestinal tract stores ingested nutrients in the stomach which are then delivered to the small intestine at a controlled rate to optimize their digestion and absorption. The interaction of nutrients with the small and large intestine generates feedback that slows gastric emptying, induces satiation, and reduces postprandial glycemic excursions. The mechanisms underlying these nutrient-gut interactions are complex; it has only recently been appreciated that the gut has the capacity to detect intraluminal contents in much the same way as the tongue, via activation of specific G-protein-coupled receptors, and that ensuing signaling mechanisms modulate the release of an array of gut hormones that influence gastrointestinal motility, appetite and glycemia. Interestingly, evidence from preclinical models supports a functional link between intestinal bitter taste receptor (BTRs) and gastrointestinal hormone secretion, and the outcomes of recent studies indicate that stimulation of intestinal ...
The winged helix factors Foxa1 and Foxa2 are essential members of the transcription factor network that govern secretory cell differentiation in the mammalian gastrointestinal tract.
During Phase I, Symbio Robotics conducted initial development of a robust, real-time, high-performance, low-cost perception engine made possible by recent advances in deep learning. This system identifies parts in 2D or 3D images and determines their six degree-of-freedom poses, producing a full description of a scene in a fraction of a second. For this technology to be practically useful in manuf .... ...
NT 3 ir cells belonged to the stroma cells of spleen and scattered mainly in the periarterial lymphoid sheath (PALS), lymphatic follicles and the inner wall of the blood vessels. NT-3-ir细胞属于网状细胞, 主要散布于动脉周围淋巴鞘(PALS)、淋巴小结和血管内壁 ...
A simple glass device is described acting as stopcock and winch at the same time. The device is especially suitable for the dislocation of solid sample holders in IR cells.
Secretory and electrophysiological properties of STC-1 cells, a cholecystokinin-secreting cell line, were examined with a radioimmunoassay and patch-clamp recording techniques. Stimulation of cholecystokinin secretion was seen after exposure to agents anticipated to increase the level of intracellular calcium, including thapsigargin (8 muM), bombesin (50 nM), potassium-induced depolarization (50 mM), or after blockade of potassium channels with barium chloride (2 mM). The secretory effects of these agents were blocked by pretreatment with the calcium channel blocker diltiazem (1 muM).
In this study we studied two aspects of enterochromaffin cell function; the nature of both the acute and chronic response to increased glucose availability. We demonstrate using intact tissue preparations and single cell approaches that acute increases in glucose, at levels found in the gut lumen rather than in plasma, trigger Ca2+ entry and 5-HT secretion in EC cells. Furthermore, this increased 5-HT release occurs through an increase in the amount of 5-HT released from vesicles in each exocytosis event. The effects of a more chronic exposure to high glucose, this time at levels akin to those observed in plasma post-prandially, cause a reduction in the synthesis and release of EC cell 5-HT. Thus EC cells respond in a diverse manner to different glucose concentrations over different periods of time to either increase or suppress 5-HT output.. Our data in intact colon tissue is the first ex vivo demonstration that EC cells are glucose-sensing cells. This is in agreement with earlier findings in ...
Ussher, J. R., Campbell, J. E., Mulvihill, E. E., . Baggio, L. L., Bates, H. E., McLean, B. A., Gopal, K., Capozzi, M., Yusta, B., Cao, X., Ali, S., Kim, M., Kabir, M. G., Seino, Y., Suzuki, J., Drucker, D. J. Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes Following Experimental Myocardial Infarction Cell Metabolism 2017 27: https://doi.org/10.1016/j.cmet.2017.11.003 Drucker, D. J., Habener, J.F., Holst J.J. Discovery, characterization and clinical development of the glucagon-like peptides J Clin Invest 2017 127(12):4217-4227. Lebrun, L.J., Kaatje Lenaerts, J., Kiers, D., Pais de Barros, J.-P., Le Guern,N., Plesnik, J., Thomas, C., Bourgeois, T., Dejong, C.H.C., Kox, M., Hundscheid, I.H.R., Khan, N.A., Mandard, S., Deckert, V., Pickkers, P., Drucker, D. J., Lagrost, L., Grober, J. Enteroendocrine cells sense LPS after gut barrier injury to enhance GLP-1 secretion Cell Reports Oct 31 2017: 21(5) 1160-1168 Baggio, L.L., Ussher, J.E., McLean, B.A., Cao, ...
Ever since FABP5 was first identified as a novel keratinocyte protein highly upregulated in psoriatic skin (22), broad and diverse roles of FABP5 such as neurogenesis (25), protective effect from lipotoxic injury (20), carcinoma cell growth (12), mammary tumorigenesis (19), and keratinocyte differentiation (4) have been elucidated. Maeda et al. (24) found that deletion of FABP5 in mice resulted in reduction in body weight gain and improvement of insulin sensitivity under HFD. They emphasized the function of FABP5 in adipocytes on the grounds that adipocytes isolated from FABP5−/− mice exhibited enhanced insulin sensitivity and that mice with adipocyte-specific overexpression of FABP5 displayed increased systemic insulin resistance. However, the possibility that FABP5 expressed in other cell types is crucial for the phenotype of FABP5−/− mice cannot be excluded given the wide range of FABP5 expression in other tissues, including skin (31), lung (30.7), and brain (21).. Very recently, ...
The gastrointestinal (GI) tract includes a diverse group of physiological features, including peristalsis, immune system protection, and nutrient absorptions. applications. We could actually identify many ground-breaking discoveries inside our review, while even more work is required to promote the scientific translation of gut bioengineering. solid course=kwd-title Keywords: Gut bioengineering, stem cells, organoids, gut fix, pharmaceutical research, laboratory on the chip Introduction Features from the gastrointestinal (GI) system mainly include meals digestive function PF-562271 ic50 and absorption of nutrition for support of day to day activities. These features are mediated with a diverse group of cells in different layers of the GI wall. The GI wall consists of mucous, submucous, muscular, and serosal layers.1,2 In the small intestine, for example, the mucous coating contains absorptive enterocytes, goblet cells, enteroendocrine cells, Paneth cells, stem cells, PF-562271 ic50 ...
Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure. To regulate food consumption, the brain must modulate appetite, and the core of appetite regulation lies in the gut-brain axis. This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells, including novel taste-like pathways. The increasingly nuanced understanding of the ...
In this weeks Nature Medicine, researchers reveal that glucagon-like peptide-1 (GLP-1), a product of proglucagon processing, may have an important role in learning and neuroprotection.. The peptide, first found in intestinal L cells of the gut, is also expressed in the brain, along with its receptor (GLP-1R). This prompted principal investigator Colin Haile, Jefferson Medical College, Philadelphia, to investigate the role of GLP-1 in neurons. Working with an international group of collaborators, Haile and first author Matthew During looked for potential neurologic roles for the peptide. When they administered it to rats, the authors found that the animals performed better than controls in a variety of learning tasks. In the Morris water maze, for example, rats directly injected in the brain with 0.1 micrograms of GLP-1 traveled much shorter distances (about two meters on average) than untreated littermates (about 10 meters) in search of the hidden platform.. To further investigate the role of ...
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Connect and collaborate with Vladimir Kopysov at Photochemistry Center RAS, with research interests in Optical Spectroscopy Optical Properties of Dyes Optical Chemosensing, on Mendeley.
M059K cells were isolated from a tumor specimen from a 33 year-old male patient with untreated glioblastoma. These cells were isolated concurrently from the same tumor specimen as M059J (see ATCC CRL-2366). -
anti-Stanniocalcin 2/STC-2, Polyclonal, Novus Biologicals 0.1mL; Unlabeled Life Sciences:Antibodies:Primary Antibodies:Immunocytochemistry (ICC)
The cellular localization of gastrin in the rabbit pyloric antrum was established by immunofluorescence. The gastrin cell was argyrophil (Grimelius technique) and identical with a previously described cell type that emits fluorescence upon combined formaldehydeozone treatment, a feature that has been interpreted as indicating storage of peptides with NH2-terminal tryptophan. The identity of the peptides and its relation to gastrin is unknown.
Taste receptors coupled to the gustatory G-protein, gustducin, on enteroendocrine cells sense nutrients to regulate gut hormone release. During Roux-en-Y gastric bypass (RYGB) surgery, the altered nutrient flow to more distal regions can affect gustducin-mediated gut hormone release and hence energy and glucose homeostasis. We studied the role of gustducin-mediated signaling in the metabolic improvements and intestinal adaptations along the gut after RYGB surgery in wild-type (WT) and α-gustducin−/− (α-gust −/−) mice. RYGB surgery decreased body weight in WT and α-gust −/− mice, whereas food intake was only decreased in WT mice. Pair-feeding to the RYGB group improved glucose homeostasis to a similar extent in WT mice. GLP1 levels were increased in both genotypes, PYY levels in α-gust −/− mice and octanoyl ghrelin levels were not affected after RYGB surgery. In WT mice, nutrients act via α-gustducin to increase L-cell differentiation (foregut) and L-cell number (foregut and ...
Over the past century, considerable progress has been made in understanding the role of enteroendocrine signals in regulating glucose. One substantial advance was the delineation of the the incretin effect, which refers to the ability of orally administered glucose to stimulate pancreatic insulin secretion to a greater extent than glucose administered intravenously.1 Glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide are the two key enteroendocrine factors responsible for the incretin effect.2 GLP-1, secreted from the lower gastrointestinal tract L-cells after nutrient ingestion, stimulates endogenous insulin secretion in a glucose dependent manner, inhibits postprandial glucagon release, delays gastric emptying, and increases satiety.3 However, GLP-1 is of limited therapeutic use because it is rapidly degraded by dipeptidyl peptidase 4, an enzyme produced at epithelial and endothelial membranes. In the linked systematic review and meta-analysis ...
Fkh6 was deleted from the genome of embryonic stem cells by targeting the gene with a neomycin resistance gene, the standard technique for producing knockout mice through homologous recombination. Homozygous null mice (Fkh6−/−) did not express Fkh6 mRNA. Importantly, they also displayed changes in gastrointestinal epithelial cell proliferation and differentiation. Normally in fetal mice, the small intestine develops from a stratified into a columnar epithelium. This transition is associated with the invagination and condensation of mesenchyme. Rudimentary villi then grow, the timing of which was delayed in the Fkh6−/− mice. When villi did appear, they were less well developed and were shorter, wider and fewer in number. Although all four epithelial cell types (enterocytes, goblet cells, enteroendocrine cells, and Paneth cells) were present in the null mice, goblet cell numbers were increased in the proximal intestine. Normally there are fewer goblet cells in the proximal than in the ...
Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5-CANNTG-3. Associates with the p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. Contributes to the regulation of several cell differentiation pathways, like those that promote the formation of early retinal ganglion cells, inner ear sensory neurons, granule cells forming either the cerebellum or the dentate gyrus cell layer of the hippocampus, endocrine islet cells of the pancreas and enteroendocrine cells of the small intestine. Together with PAX6 or SIX3, is required for the regulation of amacrine cell fate specification. Also required for dendrite morphogenesis and maintenance in the cerebellar cortex. Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis.
The potential role of the intestinal microbiota in modulating visceral pain has received increasing attention during recent years. This has led to the identification of signaling pathways that have been implicated in communication between gut bacteria and peripheral pain pathways. In addition to the well-characterised impact of the microbiota on the immune system, which in turn affects nociceptor excitability, bacteria can modulate visceral afferent pathways by effects on enterocytes, enteroendocrine cells and the neurons themselves. Proteases produced by bacteria, or by host cells in response to bacteria, can increase or decrease the excitability of nociceptive dorsal root ganglion (DRG) neurons depending on the receptor activated. Short chain fatty acids generated by colonic bacteria are involved in gut-brain communication, and intracolonic short chain fatty acids have pro-nociceptive effects in rodents but may be anti-nociceptive in humans. Gut bacteria modulate the synthesis and release of ...
Scuola di Specializzazione in Anatomia Patologica: docente di Tecniche cito-istologiche e ultrastrutturali (10 ore). ELENCO PUBBLICAZIONI. 1. BORDI C., PILATO F., CARFAGNA G., FERRARI C., DADDA T., SIVELLI R., BERTELE A., MISSALE G.: Argyrophil cell hyperplasia of fundic mucosa in patients with chronic atrophic gastritis. Digestion 35 (suppl. 1): pp. 130-143, 1986. 2. BORDI C., FERRARI C., DADDA T., PILATO F., CARFAGNA G., BERTELE A., MISSALE G.: Ultrastructural characterization of fundic endocrine cell hyperplasia associated with atrophic gastritis and hypergastrinaemia. Virchows Archiv [Pathological Anatomy] 409: 335-347, 1986. 3. BORDI C., PILATO F., CARFAGNA G., DADDA T.: Marcatori istochimici ed immunoistochimici nello studio delle lesioni precancerose endocrine dello stomaco. In I markers tumorali, F. Corrado, C. Maltoni, C. Ferri, G. Paladini, G.L. Buraggi, D. Carretti, ed., Monduzzi Editore, Bologna, 151-154, 1986. 4. DADDA T.: Caratterizzazione ultrastrutturale di lesioni ...
Recent advances possess identified metabolic reprogramming as an fundamental mechanism for cancer drug resistance. The email address details are proven as means SD, n = 6. After that we used an inhibitor of ACAT-1, avasimibe, and examined its efficiency in Mia PaCa-2 and G3K cells. The outcomes present that avasimibe successfully suppresses cell viability of both Mia PaCa-2 and G3K cells with IC50s of 7.0 and 8.85 M, respectively (Fig 1E). On the other hand, the IC50s of gemcitabine in Mia PaCa-2 and G3K cells are 1.23 and 36.34 M, respectively (Fig 1F), indicating G3K cells are highly resistant to gemcitabine. These outcomes show a higher antitumor efficiency of avasimibe also in gemcitabine resistant tumor cells. Mix of avasimibe and gemcitabine displays synergistic impact 0.05, ** 0.01, *** 0.001. Avasimibe overcomes gemcitabine-resistance by downregulating Akt pathway To research the potential systems where avasimibe overcomes gemcitabine level of resistance, weve performed immunoblotting ...
Kit contents: 1. MICROTITER PLATE * 1 2. ENZYME CONJUGATE*1 vial 3. STANDARD A*1 vial 4. STANDARD B*1 vial 5. STANDARD C*1 vial 6. STANDARD D*1 vial 7. STANDARD E*1 vial 8. STANDARD F*1 vial 9. SUBSTRATE A*1 vial 10. SUBSTRATE B*1 vial 11. STOP ...
Complex mixtures, commonly encountered in metabolomics and food analytics, are now routinely measured by nuclear magnetic resonance (NMR) spectroscopy. Since many samples must be measured, one-dimensional proton (1D 1H) spectroscopy is the experiment of choice. A common challenge in complex mixture 1H NMR sp Lab on a Chip Recent Open Access Articles
Aid, Antibodies, Biology, Endocrine Cells, Endoderm, Mice, Insulin, Cell, Cells, Adults, Manganese, Oxygen, Superoxide, and Administration