In order to assess the functional properties of human pancreatic islets we have evaluated insulin secretion, glucose metabolism and insulin mRNA synthesis. Particular attention was given to evaluate how culture and exposure to high glucose concentrations "in-vitro" influence the subsequent function of these cells. Islets were cultured for 1 and 7 days at 5.5 or 16.7 mM glucose concentrations. Insulin response to glucose, glucose+forskolin and leucine+glutamine was evaluated in freshly isolated and cultured islets. Catabolism of D-glucose was studied measuring D-(6-14C) glucose oxidation and D-(5-3H) glucose utilization. Northern blot analysis was performed to measure insulin mRNA levels. In freshly isolated islets there a low insulin response to all stimulus, but especially to nutrient secretagogues. Total glucose utilization was also lower than expected, with preferential disturbances in mitochondrial oxidative events. Independently of glucose concentration, culture improved insulin release, glucose catabolism and especially glucose oxidation, and insulin mRNA synthesis. After 7-days culture, high glucose concentration in the medium exerted beneficial effects on the overall functional activities of human pancreatic islets. Our study, 1) indicates that functional properties, initially impaired in freshly isolated human islets, improve after culture and become comparable to those previously proposed for rodent islets; and 2) argues against high glucose concentrations producing a deleterious effect on human beta-cell function. Rather they point to the concept that high glucose levels are beneficial for human islets function after long-term exposure in-vitro.