Mechanism of Gramicidin D-Induced Insulin Secretion From BTC3 Cells

Simple item page
dc.creatorDibas, Adnan I.
dc.date.accessioned2019-08-22T20:33:23Z
dc.date.available2019-08-22T20:33:23Z
dc.date.issued1995-08-01
dc.date.submitted2013-07-17T07:42:56-07:00
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.identifier.urihttps://hdl.handle.net/20.500.12503/28513
dc.language.isoen
dc.provenance.legacyDownloads0
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
dc.type.materialtext
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

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
Dibas_MechanismsOfGramicidinD.pdf
Size:
59.62 MB
Format:
Adobe Portable Document Format
Download

Collections

School of Biomedical Sciences
Theses and Dissertations