Time-course of altered islet phospholipids and of calcium binding and ionophoretic properties of islet lipids following glucose stimulation |
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Institution: | 1. Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin-Madison, Madison, WI, USA;2. William S. Middleton Memorial Veterans Hospital, Madison, WI, USA;3. Department of Medicine, Boston University School of Medicine, Boston, MA, USA;4. Departments of Internal Medicine (Endocrinology) and Cellular & Molecular Physiology, Yale University, New Haven, CT, USA;5. Molecular Nutrition Unit and Montreal Diabetes Research Center, CRCHUM, and Departments of Nutrition, Biochemistry and Molecular Medicine, Université de Montréal, Montréal, ON, Canada;1. Advanced Diagnostics, Toronto General Hospital Research Institute, Toronto, ON M5G 1L7, Canada;2. Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada;3. Departments of Medicine and Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada |
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Abstract: | The time-course of alteration in islet cell phospholipid content following d-glucose exposure in islet cells and in islet cell membranes was related to the ability of lipids extracted from both cultured pancreatic islet cells and from plasma membranes isolated from the islet cells to translocate calcium in two model membrane systems. The first model system (bulk-phase system) detected lipid species with the ability to bind calcium, irrespective of their ability to enhance calcium transport across cell membranes. The second system (multilamellar membrane system) detected lipid species with the ability to both bind calcium and to enhance calcium transport across cell membranes (true ionophores). Pre-exposure to high d-glucose concentration led to a rapid (within 1 min) fall in membrane phosphoinositides. This was partially blocked by mannoheptulose. A concurrent fall in calcium bindig activity of lipids from the plasma membrane was observed. In the whole islet cell fraction, d-glucose induced a marked increase in Ca2+ ionophoretic activity. Unlike the fall in membrane polyphosphoinositides and membrane Ca2+ binding activity, these changes were dependent on the presence of added extracellular calcium. l-Glucose was without effect on membrane phosphoinositide content. It is concluded that altered membrane and intracellular phospholipids may contribute to the increased availability of intracellular Ca2+ following d-glucose stimulation by virtue of theie Ca2+ binding and ionophoretic properties. |
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