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dc.creatorDibas, Adnan I.
dc.date.accessioned2019-08-22T20:33:23Z
dc.date.available2019-08-22T20:33:23Z
dc.date.issued1995-08-01T00:00:00-07:00
dc.date.submitted2013-07-17T07:42:56-07:00
dc.identifier.urihttps://hdl.handle.net/20.500.12503/28513
dc.description.abstractDibas, Adnan I., Mechanism of Gramicidin D-Induced Insulin Secretion From BTC3 cells. Doctor of Philosophy (Biomedical Sciences), August, 1995, 190 pp., 5 tables, 38 illustrations, bibliography, 265 titles. Gramicidin D, a sodium ionophore, was discovered to be a potent insulin secretagogue in the B-cell line BTC3 cells. Gramicidin D (1 uM) induced a 3.28-fold increase in insulin release relative to control, and when studied in a dynamic cell-perifusion system, was biphasic. Insulin secretion was accompanied by effects of gramicidin D to increase intracellular concentrations of Na+([Na+]i) and Ca2+ ([Ca2+)i) in BTC3 cells as determined by dynamic single-cell video imaging techniques, gramicidin D had no effect on cellular pH. The mechanism of gramicidin D-induced increase in [Ca2+ and suggested to be mediated by a combination of membrane depolarization-induced activation of voltage-sensitive Ca2+ channels and the activation of a Na+/Ca2+ exchanger in the reverse mode. Gramicidin D-induced increase in [Ca2+]I in the first phase correlated temporally with a profound (5.56-fold) activation of multifunctional Ca2+/calmodulin-dependent protein kinase II. While these observations are consistent with the involvement of this enzyme in gramicidin D-induced insulin secretion, further observations suggested that the kinase may play only a modulatory role in insulin secretion. A similar activation of myosin light chain kinase was not detected. In contrast to BTC3 cells, gramicidin D failed to induce insulin secretion from pancreatic islets. BTC3 cells and pancreatic islets exhibited distinct responses to ouabain, an inhibitor of the Na+/K+ ATPase, with respect to [Ca2+]I and insulin secretion suggesting that different mechanisms controlling Na+ homeostasis exist in these B-cell preparations. Furthermore, Na+/K+ ATPase activity in BTC3 cell membranes was found to be approximately fifty percent that of primary B-cells. Gramicidin D was identified as a secretagogue in BTC3 cells with a novel mechanism of action. The ability of this ionophore to induce insulin secretion from these cells and not primary B-cells is thought to be a function of different mechanisms of Na+ homeostasis and documents a functional difference in this insulinoma cell line.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectCells
dc.subjectCellular and Molecular Physiology
dc.subjectChemicals and Drugs
dc.subjectLife Sciences
dc.subjectMedical Cell Biology
dc.subjectMedicine and Health Sciences
dc.subjectMicrobiology
dc.subjectMolecular Biology
dc.subjectGramicidlin D-Induced Insulin Secretion
dc.subjectBTC3 Cells
dc.subjectsodium ionophore
dc.subjectB-cells
dc.subjectNa+ homeostasis
dc.subjectinsulin secretion
dc.titleMechanism of Gramicidin D-Induced Insulin Secretion From BTC3 Cells
dc.typeDissertation
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy
dc.type.materialtext
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