Protection of the pancreatic β-cell glucoreceptor mechanism for insulin secretion during culture in chemically defined medium

Abstract

High concentrations of glucose have a protective effect on the glucoreceptor mechanism for insulin secretion during culture of pancreatic islets in chemically defined media. To study at what level glucose exerts this effect, insulin secretion from beta-cell-rich mouse pancreatic islets was measured before and after culture for 1 week in the presence of different substances. Before culture, glucose and inosine were potent stimulators, mannose and fructose were less potent and xylitol had no effect on secretion. Culture in 3mm-glucose resulted in a 10-fold decrease in the insulin response to glucose stimulation. A less marked decrease was noted after culture in 20mm- or 30mm-glucose. Inosine-stimulated secretion was much decreased after culture in high concentrations of glucose, whereas the responses to mannose or fructose were unchanged. After culture in 30mm-mannose, glucose-stimulated secretion was similar to that observed after culture in high concentrations of glucose, whereas the response to mannose had much decreased. There were no secretory responses to glucose or fructose after culture in 30mm-fructose, or to glucose or xylitol after culture in 30mm-xylitol. Culture in 10mm-inosine did not preserve any significant response to glucose or inosine. The insulin contents of islets and culture media were higher after culture in high concentrations of glucose, mannose or inosine than after culture in fructose, xylitol or low concentrations of glucose. It is suggested that glucose, and to some extent mannose, preserves the glucoreceptor mechanism for insulin secretion by influencing an early stage in glucose metabolism, presumably glucokinase activity.