Correlated oscillations in glucose consumption, oxygen consumption, and intracellular free Ca2+ in single islets of Langerhans

Abstract

Micron-sized sensors were used to monitor glucose and oxygen levels in the extracellular space of single islets of Langerhans in real-time. At 10 mM glucose, oscillations in intraislet glucose concentration were readily detected. Changes in glucose level correspond to changes in glucose consumption by glycolysis balanced by mass transport into the islet. Oscillations had a period of 3.1 ± 0.2 min and amplitude of 0.8 ± 0.1 mM glucose (n = 21). Superimposed on these oscillations were faster fluctuations in glucose level during the periods of low glucose consumption. Oxygen level oscillations that were out of phase with the glucose oscillations were also detected. Oscillations in both oxygen and glucose consumption were strongly dependent upon extracellular Ca2+ and sensitive to nifedipine. Simultaneous measurements of glucose with intracellular Ca2+ ([Ca2+](i)) revealed that decreases in [Ca2+](i) preceded increases in glucose consumption by 7.4 ± 2.1 s during an oscillation (n = 9). Conversely, increases in [Ca2+](i) preceded increases in oxygen consumption by 1.5 ± 0.2 s (n = 4). These results suggest that during oscillations, bursts of glycolysis begin after Ca2+ has stopped entering the cell. Glycolysis stimulates further Ca2+ entry, which in turn stimulates increases in respiration. The data during oscillation are in contrast to the time course of events during initial exposure to glucose. Under these conditions, a burst of oxygen consumption precedes the initial rise in [Ca2+](i). A model to explain these results is described.