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Title: Properties of incretin hormone secreting cells : a primary cells study
Author: Habib, A. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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Incretins GLP-1 and GIP are glucose regulating peptides released from L cells and K cells in the intestine in response to food intake. They act on pancreatic β-cells to potentiate glucose-stimulated insulin release. However, incretins also play a role in regulating body weight: GLP-1 promotes weight loss by acting as a satiety signal, whereas GIP is associated with weight gain by promoting adiposity. The association between incretins and obesity/diabetes highlights the need to identify physiological signals that control their release; however this has been hampered because of our lack of a handle on these cells. Here, we report that using tissues from transgenic mice with L cell-specific or K cell-specific expression of a fluorescent protein, these rare cell populations can be highly purified and changes in their total number and/or gene expression profile (e.g. in obesity) can be monitored by FACS and quantitative RT-PCR. We have developed a cell culture system to maintain L cells and K cells in vitro. This system is suitable to characterize these cells by electrophysiology, calcium imaging, hormone secretion studies and these cells are conducive to adenoviral transfection. Affymetrix based comparative global gene expression profiles indicated that L cells from the small intestine share more commonality to K cells than to L cells in the colon. Furthermore, we have identified a number of candidate sensors for dietary fatty acids, amino acids or glucose as well as signalling pathways preferentially expressed in L cells and/or K cells. A better understanding of these genes and pathways may help us to determine how the levels of these important hormones can be modulated in patients with type 2 diabetes and obesity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available