Can desensitization of the B-cell to D-glucose be simulated in cultured pancreatic islets?

Abstract

In order to investigate the phenomenon of B-cell desensitization to D-glucose, rat pancreatic islets were cultured for 20-44h in the presence of increasing concentrations of D-glucose in the 5.6 to 27.8 mM range, and then incubated for 30 to 120 min for measurement of secretory, metabolic and ionic variables. After culture in the presence of 5.6 mM D-glucose, the release of insulin evoked by D-glucose (16.7 mM) was less marked than that seen in islets cultured in the presence of 11.1 mM D-glucose. In the latter islets, the secretory response to D-glucose (8.3 mM or more) was still modest, especially over short periods of incubation, but was markedly enhanced by either theophylline or forskolin. The release of insulin evoked by D-glucose in the presence of theophylline was little affected by either Ca2+ concentration of the culture medium or length of culture period (20h vs 44h). The culture-induced alteration in the responsiveness to D-glucose coincided with a smaller relative increase of D-[5(3)H]glucose utilization, D-[U-14C]glucose oxidation or net 45Ca uptake at increasing concentrations of the hexose. It contrasted with a well-preserved secretory response to nonnutrient secretagogues. Although these findings could be interpreted as evidence of B-cell desensitization to D-glucose, the fact that the secretory behavior of the islets was not vastly different whether they were first cultured at physiological (8.3 mM) or higher (11.1 to 27.8 mM) concentrations of D-glucose suggests that this experimental design may not be an optimal model for the functional alteration of the B-cell in hyperglycemic non-insulin-dependent diabetic subjects.