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

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.

[1]  A. Yates,et al.  Effects of lactate on pancreatic islets. Lactate efflux as a possible determinant of islet-cell depolarization by glucose. , 1989, The Biochemical journal.

[2]  Bo Hellman,et al.  Glucose-induced oscillations of cytoplasmic Ca2+ in the pancreatic β-cell , 1988 .

[3]  K Eschrich,et al.  Sustained oscillations in a reconstituted enzyme system containing phosphofructokinase and fructose 1,6-bisphosphatase. , 1983, Archives of biochemistry and biophysics.

[4]  H. Najafi,et al.  Fuel-Stimulated Insulin Secretion by Clonal Hamster β-Cell Line HIT T-15 , 1987, Diabetes.

[5]  W. Malaisse,et al.  Stimulus-secretion coupling of glucose-induced insulin release. Timing of early metabolic, ionic, and secretory events. , 1981, Metabolism: clinical and experimental.

[6]  C Olsen,et al.  An enzymatic fluorimetric micromethod for the determination of acetoacetate, -hydroxybutyrate, pyruvate and lactate. , 1971, Clinica chimica acta; international journal of clinical chemistry.

[7]  E. Sel'kov,et al.  Self-oscillations in glycolysis. 1. A simple kinetic model. , 1968, European journal of biochemistry.

[8]  R. Steiner,et al.  Cycle detection: a technique for estimating the frequency and amplitude of episodic fluctuations in blood hormone and substrate concentrations. , 1983, Endocrinology.

[9]  D. Cook,et al.  Isolated islets of Langerhans have slow oscillations of electrical activity. , 1983, Metabolism: clinical and experimental.

[10]  M. J. MacDonald,et al.  Elusive Proximal Signals of β-Cells for Insulin Secretion , 1990, Diabetes.

[11]  F M Matschinsky,et al.  Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion. , 1987, Physiological reviews.

[12]  Teller Dc,et al.  Dynamic aspects of insulin action: synchronization of oscillatory glycolysis in isolated perifused rat fat cells by insulin and hydrogen peroxide. , 1983 .

[13]  E. Gylfe,et al.  Ca2+ oscillations in pancreatic β‐cells exposed to leucine and arginine , 1989 .

[14]  W. Malaisse,et al.  Insulin release: the fuel hypothesis. , 1979, Metabolism: clinical and experimental.

[15]  W. Malaisse,et al.  The stimulus secretion coupling of glucose-induced insulin release. , 1979, Archives of biochemistry and biophysics.

[16]  B Hess,et al.  The glycolytic oscillator. , 1979, The Journal of experimental biology.

[17]  P. J. Randle,et al.  Glucose metabolism in mouse pancreatic islets. , 1970, The Biochemical journal.

[18]  F. Matschinsky,et al.  Pancreatic islet glucose metabolism and regulation of insulin secretion. , 1986, Diabetes/metabolism reviews.

[19]  J. Ross,et al.  Concentration oscillations and efficiency: glycolysis. , 1981, Science.

[20]  E. Ipp,et al.  Pulsatile Insulin Secretion in Isolated Rat Islets , 1990, Diabetes.

[21]  W. Malaisse,et al.  Measurement of lactic acid in nanomolar amounts. Reliability of such a method as an index of glycolysis in pancreatic islets. , 1976, Biochemical medicine.