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Identifier 000400995
Title Molecular characterization of duodenal CCK-containing enteroendocrine cells
Alternative Title Μοριακός χαρακτηρισμός των εντεροενδοκρινών κυττάρων χολοκυστοκινίνης του δωδεκαδάκτυλου
Author Συκαράς, Αλέξανδρος Γ.
Thesis advisor Ζαννής, Βασίλειος
Reviewer Καρδάσης, Δημήτριος
Μπούμπας, Δημήτριος
Θερμού, Κυριακή
Γραβάνης, Αχιλλέας
Τσατσάνης, Χρήστος
Γουλιέλμος, Γεώργιος
Abstract The enteroendocrine system orchestrates the physiological responses to food intake. Enteroendocrine (EEC) cells sense nutrients and secrete hormones in response to them. There are more than fifteen subtypes of EEC cells that secrete a range of gut hormones, which play a pivotal role in the co-ordination of food digestion, control of appetite and the regulation of glucose homeostasis. I-cells represent a subset of enteroendocrine cells that are mainly localized in the proximal small intestine (duodenum) and release cholecystokinin (CCK) in response to nutrients (mainly fat). CCK is the archetypal satiety hormone that transmits anorectic signals to the brain via a gut-to-brain signalling pathway, mediated by vagal afferent neurons. Additionally, CCK has a key pro-digestive function by inhibiting gastric emptying and stimulating the release of bile from the gallbladder and the secretion of pancreatic enzymes. Until recently, the characterization of enteroendocrine cells has been restricted to cell line models. The development of transgenic animal models with genetically tagged enteroendocrine cells enabled us to study native enteroendocrine cells. We used a transgenic mouse model that express enhanced Green Fluorescence Protein (eGFP) under the control of Cck gene promoter, in order to study native I-cells. Initially, we developed a robust protocol for the isolation of duodenal CCK-containing cells that represent the typical I-cells. By using semi-quantitative RT-PCR, we revealed that duodenal I-cells contain mRNA transcripts encoding key long chain fatty acid (LCFA), short chain fatty acid (SCFA) and endocannabinoid receptors. We also analysed the gut hormone content of duodenal I-cells and found that a subpopulation of CCK-containing cells co-express CCK with proglucagon, glucose-dependent insulinotropic peptide (GIP), Peptide YY (PYY), neurotensin, secretin and surprisingly the orexigenic hormone ghrelin. Our findings suggest that duodenal I-cells have the capacity to sense LCFA, SCFA, fatty acid lipid amides and intestinal endocannabinoid peptides. They also indicate that there is a significant overlap between I-cells and other subsets of EEC cells and that a subset of I-cells may co-release CCK with other gut hormones.
Language English
Subject Gut hormones
Metabolism
Receptors
Εντερικές ορμόνες
Μεταβολισμός
Υποδοχείς
Issue date 2015-11-13
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
Permanent Link https://elocus.lib.uoc.gr//dlib/e/9/5/metadata-dlib-1463652748-458101-20214.tkl Bookmark and Share
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