Relationships between energy level and insulin secretion in isolated rat islets of Langerhans. Manipulation of [ATP]/[ADP][Pi] by 2-deoxy-D-glucose

Abstract

Perifusion of islets with nominally phosphate-free buffer containing increasing concentrations of 2-deoxy-D-glucose (2.5 to 10 mM) produced increments in high alpha-ketoisocaproic acid-induced secretion of insulin beyond those observed in the absence of the sugar analogue. 3-O-methyl-D-glucose, a poorly metabolized sugar, was without effect. Insulin release evoked by 40 mM KCl was not altered by 2-deoxyglucose. The concentration of intracellular inorganic phosphate was lower in islets perifused with 2-deoxyglucose and declined to a lower level after addition of 20 mM alpha-ketoisocaproic acid. The enhancement of alpha-ketoisocaproic acid-induced hormone secretion by 2-deoxyglucose was not seen in islets perifused with medium containing 1.5 mM phosphate; instead a small inhibition was observed. It is postulated that conditions which lower intracellular [Pi] facilitate, either directly or indirectly, hormone release although the mechanism of this effect remains to be elucidated.