Thulium binding to the pancreatic beta-cell membrane

Radioactive thulium (171Tm) was used to probe cation-binding sites in the plasma membrane of beta-cell-rich pancreatic islets microdissected from noninbred ob/ob mice. Temporal studies revealed that 171Tm uptake was rapid, reaching isotopic equilibrium by 60 min. Analysis of the concentration dependence of 171Tm uptake revealed at least two components. At low 171Tm concentrations (0.003--0.18 micrometer), there was a saturable low capacity component, capable of accommodating less than 20 mumol/kg dry weight. At higher 171Tm concentrations (1.0--500 micrometers), a nonsaturable high capacity component capable of binding more than 100 mmol/kg dry weight was observed. 171Tm taken up at 0.18 micrometer exhibited a high degree of mobility. The uptake of 171Tm at this concentration was increased by incubation with chlorpromazine at concentrations known to increase the permeability of the beta-cell plasma membrane. At 0.18 micrometer, exposure to 20 mM D-glucose reduced 171Tm uptake compared with that in islets incubated in the absence of sugar or in the presence of sugars which lack stimulatory effects on insulin release. Such an effect was not observed at 125 micrometers, and none of the sugars influenced the 171Tm uptake of the exocrine pancreas. These data raise the possibility that cation-binding sites in the beta-cell plasma membrane are of physiological significance in the regulation of insulin secretion.