| 1. |
- Strickertsson, Jesper A. B., et al.
(författare)
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Interferon-gamma inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism
- 2011
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Ingår i: World Journal of Gastroenterology. - 1007-9327. ; 17:26, s. 3117-3125
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate if and how the proinflammatory cytokine interferon gamma (IFN gamma) affects ghrelin expression in mice. METHODS: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were examined in wild-type mice and mice infected with Helicobacter pylori (H. pylon). Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFN gamma alone, mice were given a subcutaneous infusion of IFN gamma for 7 d. Finally, the influence of IFN gamma, and somatostatin on the ghrelin promoter was characterized. RESULTS: H. pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models. Subcutaneous infusion of IFN gamma suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFN gamma. CONCLUSION: Gastric infection and inflammation is associated with increased IFN gamma expression and reduced ghrelin expression. IFN gamma does not directly control ghrelin expression but inhibits it indirectly via somatostatin. (C) 2011 Baishideng. All rights reserved.
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| 2. |
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| 3. |
- Friis-Hansen, Lennart, et al.
(författare)
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Characteristics of gastrin controlled ECL cell specific gene expression
- 2007
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 140:3, s. 153-161
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ECL cells are histamine-producing endocrine cells in the oxymic mucosa that synthesize and secrete proteins and peptides. They are the primary target for gastrin and mediate the control of gastrin on acid secretion and oxyntic mucosal growth. Knowledge of the molecular biology of the ECL cell is therefore important for understanding gastric physiology. Accordingly, we wanted to identify genes that are characteristically expressed in the ECL cells and controlled by gastrin. Methods: Using Affymetrix GeneChips((R)), RNA expression profiles were generated from ECL cells isolated by counterflow elutriation from hyper- or hypogastrinemic rats. Contamination from non-endocrine cells was eliminated by subtraction of the expression profiles of the fundic and antral mucosa. Results: The expression of 365 genes was ECL cell characteristic. Gastrin was found to control the expression of 120 which could be divided into two major groups depending on the known or anticipated biological function of the encoded protein: genes encoding proteins involved in the secretory process and genes encoding proteins needed to generate energy for secretion. Interestingly, gastrin stimulation also increased ECL cells expression of anti-apoptotic genes. Conclusion: The ECL cell specific expression profile is reminiscent of that of neurons and other endocrine cells exhibiting high expression of genes encoding proteins involved in the synthesis, storage and secretion of neuropeptides or peptide hormones. Gastrin regulated the expression of one third of these genes and is thus involved in the control of secretion from the ECL cells.
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| 4. |
- Friis-Hansen, Lennart, et al.
(författare)
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Gastric inflammation, metaplasia, and tumor development in gastrin-deficient mice
- 2006
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Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 131:1, s. 246-258
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Gastrin deficiency and proton pump inhibitor treatment cause achlorhydria, which predisposes to disease. To elucidate the underlying molecular biology, we examined the changes in gastric gene expression in both types of achlorhydria. We also explored the associated changes in the gastric microflora and the long-term consequences of gastrin-deficient achlorhydria. Methods: Expression profiles were generated from gastric RNA from wild-type mice, gastrin knockout (KO) mice, gastrin KO mice after I week of gastrin infusion, and wild-type mice treated for I month with a proton pump inhibitor. The results were confirmed using real-time polymerase chain reaction and immuno-histochemistry. Selective media were used to characterize the gastric microflora. Results: The number of gastric bacteria was increased in both gastrin KO and PPI-treated mice. The expression profiles revealed activation of immune defense genes, interferon-regulated response genes, and intestinal metaplasia of the gastric mucosa. In young gastrin-deficient mice, gastrin infusions reversed the changes. Over time, the changes accumulated, became irreversible, and progressed into metaplasia and polyp development. Finally, the study showed that gastrin regulated the expression of genes encoding extracellular matrix proteins. Conclusions: Independently of gastrin, achlorhydria is associated with gastric bacterial overgrowth and intestinal gene expression patterns and is associated with predisposition to disease. Gastrin is therefore essential for prevention of gastric disease, mainly through control of acid secretion but to a lesser extent also through control of gastric gene expression. The gastrin-deficient mouse serves as a useful new model for gastric metaplasia and neoplasia.
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| 5. |
- Friis-Hansen, Lennart, et al.
(författare)
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Reduced ghrelin, IAPP and PYY expression in the stomach of gastrin-cholecystokinin knockout mice.
- 2005
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 146:10, s. 4464-4471
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Tidskriftsartikel (refereegranskat)abstract
- The antral hormone gastrin and its intestinal relative, cholecystokinin (CCK), are pivotal in the regulation of gastric functions. Other gastric hormones like ghrelin, peptide YY (PYY), and islet amyloid polypeptide (IAPP), however, also contribute to the regulation of acid secretion, motility, and feeding. Because gastrin and CCK are crucial for gastric homeostasis, we examined how loss of gastrin alone and gastrin plus CCK affected the expression of ghrelin, IAPP, and PYY and ghrelin secretion. The expression of ghrelin, IAPP, and PYY and the CCK-A receptor genes were examined in both gastrin and gastrin-CCK double-knockout (KO) mice using immunocytochemistry and quantitative RT-PCR. Ghrelin concentrations in plasma were measured using RIA. Gastrin and CCK were infused in gastrin-CCK KO mice using osmotic minipumps. The number of ghrelin cells and ghrelin gene expression were unaffected, albeit the ghrelin cells were located closer to the base of the glands in both KO mouse strains when freely fed. However, lack of both gastrin and CCK attenuated fasting-induced ghrelin expression and secretion. Fundic ghrelin cells expressed the CCK-A receptor, and ghrelin expression increased after CCK infusion. Furthermore, gastric IAPP and PYY expression as well as the number of IAPP- and PYY-containing cells were reduced in both gastrin and gastrin-CCK KO mice. Gastrin infusion increased gastric IAPP but not PYY expression. In conclusion, lack of gastrin plus CCK but not gastrin alone reduced ghrelin secretion in response to fasting through both direct and indirect mechanisms. Both gastrin and combined gastrin-CCK deficiency reduced the gastric IAPP and PYY expression.
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| 6. |
- Fåk, Frida, et al.
(författare)
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Gastric ghrelin cell development is hampered and plasma ghrelin is reduced by delayed weaning in rats
- 2007
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 1479-6805 .- 0022-0795. ; 192:2, s. 345-352
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Tidskriftsartikel (refereegranskat)abstract
- The duration of breastfeeding has attracted much interest, as a prolonged period of breastfeeding has been shown to reduce the risk of developing obesity. The mechanism behind the reduced risk is, however, poorly understood. The novel hormone ghrelin augments appetite, promotes body. weight increase and increases adiposity. The majority of circulating ghrelin emanates from endocrine cells in the oxyntic mucosa of the stomach. In newborn humans and rodents, the number of ghrelin cells is low after birth until weaning, when the cell population is greatly expanded. To date, information about the influence of weaning perturbations on ghrelin cell development is scarce. Therefore, we studied the effect of delayed weaning on gastric ghrelin expression and plasma ghrelin concentration. To this end, special food separator cages were used to prevent the pups from eating solid food, forcing them to drink milk up to 21 days of age. Gastric ghrelin expression was examined by immunocytochemistry and in situ hybridisation, and plasma concentrations were assessed by RIA. Our data showed that gastric ghrelin expression and plasma ghrelin concentration are maintained at a lower level by delayed weaning. We also found that the relation between gastric ghrelin expression and body weight was altered by delayed weaning. Thus, control rats displayed a positive correlation between ghrelin expression and body weight, while no such correlation was evident in animals with delayed weaning. We conclude that delayed weaning exerts a negative influence on ghrelin expression, and that the onset of solid food intake may trigger normal ghrelin expression. Therefore, we suggest that ghrelin may constitute a hormonal link between the duration of breastfeeding and body weight development.
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| 7. |
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| 8. |
- Ringström, Camilla, et al.
(författare)
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Apelin is a novel islet peptide.
- 2010
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 162, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- Apelin, a recently discovered peptide with wide tissue distribution, regulates feeding behavior, improves glucose utilization, and inhibits insulin secretion. We examined whether apelin is expressed in human islets, as well as in normal and type 2 diabetic (T2D) animal islets. Further, we studied islet apelin regulation and the effect of apelin on insulin secretion. Apelin expression and regulation was examined in human and animal specimens using immunocytochemistry, in situ hybridization, and real-time PCR. Insulin secretion was studied in INS-1 (832/13) clonal beta cells. APJ-receptor expression was studied using real-time PCR. In human and murine islets apelin was predominantly expressed in beta cells and alpha cells; a subpopulation of the PP cells in human islets also harbored apelin. In porcine and feline islets apelin was mainly expressed in beta cells. APJ-receptor expression was detected in INS-1 (832/13) cells, and in human and mouse islets. A high dose (1microM) of apelin-36 caused a moderate increase in glucose-stimulated insulin secretion (30%; p<0.001), while lower concentrations (10-100nM) of apelin robustly reduced insulin secretion by 50% (p<0.001). Apelin was upregulated in beta cells of T2D db/db mice (47% vs. controls; p<0.02) and GK-rats (74% vs. controls; p<0.002), but human islet apelin expression was unaffected by glucose. On the other hand, human islet apelin expression was diminished after culture in glucocorticoids (16% vs. controls; p<0.01). We conclude that apelin is a novel insulin-regulating islet peptide in humans and several laboratory animals. Islet apelin expression is negatively regulated by glucocorticoids, and upregulated in T2D animals. The presence of apelin receptors in islets suggests a role for apelin as a paracrine or autocrine messenger within the islets.
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| 9. |
- Strickertsson, Jesper A. B., et al.
(författare)
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Enterococcus faecalis Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA). Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Mitochondrial mutations were determined by sequencing. Results: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos). Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. Conclusions: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-kappa B inflammatory response as well as impaired DNA damage response and cell cycle control gene expression.
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| 10. |
- Åstrand, Ramona, et al.
(författare)
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Comparison between capillary, venous and arterial levels of protein S100B in patients with severe brain pathology
- 2012
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 50:6, s. 1055-1061
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Tidskriftsartikel (refereegranskat)abstract
- Background: Protein S100B is soon in clinical use as a sensitive marker after mild traumatic head injury in adults. Initial studies of S100B in pediatric head injury have shown promising results. Venous sampling can be challenging in children and capillary samples are often a preferred option. The aim of the study was to investigate the relation between capillary, venous and arterial measurements of protein S100B, primarily by determining whether capillary S100B differ from venous and if capillary S100B can predict venous S100B levels, and secondarily, if arterial S100B samples can substitute venous samples in severely brain-injured patients. Methods: Venous, arterial and capillary blood samples for S100B were collected simultaneously once a day for a maximum of 6 days. Patients were >= 18 years old and admitted to neurointensive care due to severe brain pathology. Results: Capillary S100B samples were on average 0.08 mu g/L higher than venous S100B samples. Prediction of venous concentration from capillary samples yielded a prediction error of 0.07 mu g/L. The mean difference between venous and arterial samples was 0.01 mu g/L. The mean prediction error was 0.03 mu g/L. Conclusions: Capillary and venous serum S100B are not interchangeable, and should be considered as two separate, although related, variables. Arterial measurements of S100B can successfully predict the corresponding venous concentration.
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