Abstract
Phlorizin (10 mM) inhibited glucose-stimulated insulin release from microdissected pancreatic islets of obese-hyperglycemic mice. In the absence of glucose, phlorizin (5-15 mM) as well as phloretin (10 mM) stimulated insulin release. These stimulatory effects were inhibited by mannoheptulose, suggesting that phlorizin and phloretin were sensed by the system which recognizes glucose as an insulin secretagogue. However, the mechanism sensitive to phlorizin does not seem to possess the full competence of the glucose-recognizing system, since phlorizin did not potentiate the insulin-releasing actions of arginine or theophylline. Leucine, but not pyruvate or succinate, enhanced the stimulatory effect of phlorizin. Radioactive phlorizin rapidly accumulated in amounts far exceeding the urea space of the islets. This uptake was concentration-dependent up into the millimolar concentration range. It was not significantly influenced by glucose. Antimycin A, p-chloromercuriphenyl-sulfonic acid, and chlorpromazine, which increase the uptake of extracellular space markers, stimulated the uptake of phlorizin in whole islets but not in islet homogenates. It is suggested that phlorizin binds predominantly to the plasma membranes of intact β-cells. Although the binding may not be specific for glucose sites, reaction with such a site could be responsible for the phlorizin-induced insulin release.
ACKNOWLEDGMENTS Radioactive phlorizin was donated by the Swedish Branch of Farbwerke Hoechst through the courtesy of Dr. H. Heise. We also thank AB Leo, Helsingborg, for a gift of chlorpromazine, and Novo A/S, Copenhagen, for preparing crystalline mouse insulin. Dr. L. Höglund, Department of Zoology, University of Umeå, kindly performed the gas chromatographic analyses of phloretin and phlorizin.
- Copyright ©, 1972, by Academic Press, Inc.
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