Oscillations of lactate released from islets of Langerhans: evidence for oscillatory glycolysis in beta-cells.

Abstract

Oscillations in the glycolytic process have been demonstrated in a number of different biological systems. However, their presence has never been demonstrated in insulin-secreting beta-cells. We used lactate as a marker for glycolysis and measured lactate and insulin concentrations in the effluent of isolated perifused rat islets of Langerhans. Sustained regular oscillations in lactate concentrations with an average period of 16-20 min were observed in islets that were perifused with medium containing 5.5 or 16.7 mM glucose. Sustained oscillations of insulin concentrations secreted by the islets were also observed in these experiments, and the average period of oscillation was 14.6 +/- 2.3 min at 16.7 mM glucose. Mean insulin concentrations at 5.5 mM glucose were too low to permit analysis of oscillations. Spectral analysis confirmed the regularity of the lactate and insulin oscillations and showed peaks that were consistent with the average periods obtained using the Clifton program. Moreover, spectral analysis demonstrated marked similarity between the patterns of lactate and insulin oscillation during perifusion with 16.7 mM glucose. Cross-correlation analysis found these oscillations not to be consistently in phase. In conclusion, sustained oscillations in lactate released from islets of Langerhans suggest that the glycolytic process in beta-cells also oscillates. The similarity of the periods of lactate and insulin raises the possibility that oscillations in glycolysis may provide a mechanism for pulsatile insulin secretion.