Sulfonylurea binding to adipocyte membranes and potentiation of insulin-stimulated hexose transport.

摘要: Abstract We have previously shown that the sulfonylureas increase insulin-stimulated glucose transport in adipocytes mainly by enhancing insulin-induced recruitment of transporter from its intracellular storage pool to plasma membrane (Jacobs, D. B., and Jung, C. Y. (1985) J. Biol. Chem. 260, 2593-2596). In order determine if this sulfonylurea effect is mediated a specific membrane-associated sulfonylurea-binding protein, present report we measured exact dose dependence enhancement activities different primary culture equilibrium binding affinities these agents various adipocyte fractions. Glycuride was found insulin-stimulated, 3-O-methyl-D-glucose exchange cultured rat up 60% with little absence insulin. The developed gradually reaching maximum level at 24 h incubation. concentration dependent showing simple, one-to-one stoichiometry an apparent activation constant (Ka) approximately 1 microM. Glypizide, tolazamide, tolbutamide also enhanced hexose 60%, but Ka 2, 11, 25 microM, respectively. HB-699 ciglitazone, non-sulfonylureas, were without under same condition. experiments, [3H]glyburide bind membranes two or more protein-specific, saturable sites, similar dissociation constants (KD) ranging 1-3 These protein-specific glyburide bindings displaced not only tolazamide tolbutamide, ciglitazone HB-699, indicated KD 11-16, 80-85, 20-25, 85-95 However, fraction, displacements partial did exceed 56-61% maximum. Based on findings, propose there sulfonylurea-specific-binding protein adipocytes, may play key role sulfonylureas, probably via potentiation transporter.