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dc.contributor.authorSmith, Catherine Maryen_US
dc.date.accessioned2017-09-07T14:20:15Z
dc.date.issued2017
dc.identifier.urihttps://hdl.handle.net/2144/23731
dc.description.abstractBACKGROUND: Post-bariatric hypoglycemia (PBH), a complication of gastric bypass surgery, is characterized by postprandial hyperinsulinemic hypoglycemia. To date, the etiology of PBH has not been fully elucidated. OBJECTIVE: To develop a murine model of PBH by experimentally modifying candidate molecules identified in humans with PBH. METHODS: Gastric bypass patients were assigned to groups based on whether or not they suffered from hypoglycemia (PBH, n = 11; asymptomatic, n = 7). Patients underwent a mixed meal tolerance test with blood draws at baseline, 30 minutes, and 120 minutes postprandially. SOMAscan (Somalogic) was used to evaluate serum for protein levels. In parallel, mass spectrometry (Metabolon) was used to examine metabolite levels. Mice were treated with the Farnesoid X Receptor (FXR) agonist, fexaramine (Fex), or vehicle for 5 days before undergoing a glucose tolerance test (GTT). Mice were sacrificed with tissues collected immediately thereafter. PCR was performed to quantify expression of FXR target genes. A separate cohort of mice was treated with adenine or vehicle for 2 days before undergoing a GTT or an insulin tolerance test. RESULTS: FGF19 was the most significantly upregulated protein in the PBH group at all time points. At 120 minutes postprandially, FGF19 was 2.1-fold higher in the PBH group (p < 1x10-5). Adenine was >2-fold higher at all time points (p < 1x10-8). Treatment with Fex did not result in significant differences during GTT or in expression of FXR target genes. Treatment with adenine did not significantly impact glucose tolerance or insulin sensitivity between groups. CONCLUSIONS: The results of the human serum analyses established a strong foundation on which to develop a murine model of PBH. Though the mouse experiments failed to induce postprandial hypoglycemia, they have directed future experiments toward developing a murine model of PBH.en_US
dc.language.isoen_US
dc.subjectEndocrinologyen_US
dc.subjectDiabetesen_US
dc.subjectEndocrinologyen_US
dc.subjectHypoglycemiaen_US
dc.subjectBariatric surgeryen_US
dc.subjectPost bariatric hypoglycemiaen_US
dc.titleThe development of a mouse model of post-bariatric hyperinsulinemic hypoglycemiaen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2017-07-12T01:11:29Z
dc.description.embargo2018-07-11T00:00:00Z
etd.degree.nameMaster of Scienceen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Sciencesen_US
etd.degree.grantorBoston Universityen_US


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