Summary
When isolated islets of Langerhans are suddenly exposed to glucose, the entry of the hexose into islet cells first occurs at a high rate resulting in rapid equilibration of free glucose across the cell membrane; thereafter, the rate of net glucose uptake depends on its metabolism. More than 95% of the glucose taken up by the islets is converted to triosephosphate. The fractional contribution of the sorbitol and pentose-phosphate pathways to such a process does not exceed 10%. The output of lactate from the islets accounts for approximately half of the glycolytic flux. At increasing glucose concentrations up to 4.3 mM, the rate of glycolysis increases towards a first asymptotic value; at higher glucose levels (up to 27.8 mM), a sigmoidal pattern is seen tending towards a second saturation value. The total ATP content of the islets does not correlate with their insulin-secretory activity. It is suggested that, in the process of glucose-induced insulin release, glycolysis may regulate physiological processes possibly located in the micro-environment of the cell boundary.
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Ashcroft S. J. H., Capito K., Hedeskov C. J.: Time Course Studies of Glucose-Induced Changes in Glucose-6-Phosphate and Fructose-1,6-Diphosphate Content of Mouse and Rat Pancreatic Islets — Diabetologia9, 299, 1973.
Ashcroft S. J. H., Chatra L., Weerasinghe L. C. C., Randle P. J.: Interrelationship of Islet Metabolism, Adenosine Triphosphate Content and Insulin Release — Biochem. J.132, 223, 1973.
Ashcroft S. J. H., Weerasinghe L. C. C., Bassett J. M., Randle P. J.: The Pentose Cycle and Insulin Release in Mouse Pancreatic Islets — Biochem. J.126, 525, 1972.
Brisson G. R., Malaisse-Lagae F., Malaisse W. J.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. VII. A Proposed Site of Action for Adenosine-3′,5′-Cyclic Monophosphate — J. clin. Invest.51, 232, 1972.
Dean P. M., Matthews E. K., Sakamoto Y.: Pancreatic Islet Cells: Effects of Monosaccharides, Glycolytic Intermediates and Metabolic Inhibitors on Membrane Potential and Electrical Activity — J. Physiol. (Lond.)246, 459, 1975.
Hellerström C., Brolin S. E.: Energy Metabolism of the β-Cell — In:Hasselblatt A., Bruchhausen F. (Eds): Insulin II — Springer-Verlag, Berlin, 1975; p. 57.
Hellman B., Idahl L.-Å., Lernmark Å., Sehlin J., Täljedal I.-B.: The Pancreatic β-Cell Recognition of Insulin Secretagogues. Comparison of Glucose with Glyceraldehyde Isomers and Dihydroxyacetone — Arch. Biochem.162, 448, 1974.
Hellman B., Idahl L.-Å., Lernmark Å., Täljedal I.-B.: The Pancreatic β-Cell Recognition of Insulin Secretagogues: Does Cyclic AMP Mediate the Effect of Glucose? — Proc. nat. Acad. Sci. (Wash.)71, 3405, 1974.
Hellman B., Sehlin J., Täljedal I.-B.: Evidence for Mediated Transport of Glucose in Mammalian Pancreatic β-Cells — Biochim. biophys. Acta (Amst.)241, 147, 1971.
Henquin J.-C., Lambert A. E.: Cobalt Inhibition of Insulin Secretion and Calcium Uptake by Isolated Rat Islets — Amer. J. Physiol.228, 1669, 1975.
Katz J., Wood H. G.: The Use of14CO2 from Glucose-1 and 6-14C for the Evaluation of the Pathways of Glucose Metabolism — J. biol. Chem.238, 517, 1963.
Krahl M. E.: Endocrine Function of the Pancreas — Ann. Rev. Physiol.36, 331, 1974.
Landgraf R., Kotler-Brajtburg J., Matschinsky F. M.: Kinetics of Insulin Release from the Perfused Rat Pancreas Caused by Glucose, Glucosamine, and Galactose — Proc. nat. Acad. Sci. (Wash.)68, 536, 1971.
Levy J., Herchuelz A., Sener A., Malaisse W. J.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. XX. Fasting: a Model for Altered Glucose Recognition by the B-Cell — Metabolism25, 583, 1976.
Levy J., Herchuelz A., Sener A., Malaisse-Lagae F., Malaisse W. J.: Cytochalasin B-Induced Impairment of Glucose Metabolism in Islets of Langerhans — Endocrinology98, 429, 1976.
Malaisse W. J., Brisson G., Malaisse-Lagae F.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. I. Interaction of Epinephrine and Alkaline Earth Cations — J. Lab. clin. Med.76, 895, 1970.
Malaisse W. J., Herchuelz A., Levy J., Sener A., Pipeleers D. G., Devis G., Somers G., van Obberghen E.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. XIX. The Insulinotropic Effect of Glyceraldehyde — Molec. cell. Endocr.4, 1, 1976.
Malaisse W. J., Herchuelz A., Levy J., Somers G., Devis G., Ravazzola M., Malaisse-Lagae F., Orci L.: Insulin Release and the Movements of Calcium in Pancreatic Islets — In:Carafoli E., Clementi F., Drabikowsky W., Margreth A. (Eds): Calcium Transport in Contraction and Secretion. North-Holland Publ. Co., Amsterdam/Oxford, 1975; p. 211.
Malaisse W. J., Lea M. A., Malaisse-Lagae F.: The Effect of Mannoheptulose on the Phosphorylation of Glucose and the Secretion of Insulin by Islets of Langerhans — Metabolism17, 126, 1968.
Malaisse W. J., Pipeleers D. G., Levy J.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. XVI. A Glucose-Like and Calcium-Independent Effect of Cyclic AMP — Biochim. biophys. Acta (Amst.)362, 121, 1974.
Malaisse W. J., Sener A., Koser M., Herchuelz A.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. XXIV. The Metabolism of α- and β-D-Glucose in Isolated Islets — J. biol. Chem. 1976. (In press).
Malaisse W. J., Sener A., Levy J.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. XXI. Fasting-Induced Adaptation of Key Glycolytic Enzymes in Isolated Islets — J. biol. Chem.251, 1731, 1976.
Malaisse W. J., Sener A., Levy J., Herchuelz A., Devis G., Somers G.: Calcium Antagonists and Islet Function. VII. Effect of Calcium Deprivation — J. Membr. Biol. (In press).
Malaisse W. J., Sener A., Mahi M.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. XVIII. Sorbitol Metabolism in Isolated Islets — Europ. J. Biochem.47, 365, 1974.
Malaisse-Lagae F., Malaisse W. J.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. III. Uptake of45Calcium by Isolated Islets of Langerhans — Endocrinology88, 72, 1971.
Matschinsky F. M., Ellerman J. E.: Metabolism of Glucose in the Islets of Langerhans — J. biol. Chem.243, 2730, 1968.
McDaniel C. F., Kirtley M. E.: The Interaction of Glyceraldehyde-3-Phosphate B on Hexose Transport and Glucose Metabolism in Pancreatic Islets — Diabetologia10, 303, 1974.
McDaniel M. L., King S., Anderson S., Fink J., Lacy P. E.: Effect of Cytochalasin Dehydrogenase with Human Erythrocyte Membranes — J. biol. Chem.249, 6478, 1974.
Schrier S. L.: Studies of the Metabolism of Human Erythrocyte Membranes — J. clin. Invest.42, 756, 1963.
Sener A., Levy J., Malaisse W. J.: The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. XXIII. Does Glycolysis Control Calcium Transport in the B-Cell? — Biochem. J.156, 521, 1976.
Sener A., Malaisse W. J.: Measurement of Lactic Acid in Nanomolar Amounts. Reliability of Such a Method as an Index of Glycolysis in Pancreatic Islets — Biochem. Med.15, 34, 1976.
Shin B. C., Carraway K. L.: Association of Glyceraldehyde-3-Phosphate Dehydrogenase with the Human Erythrocyte Membrane — J. biol. Chem.248, 1436, 1973.
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Malaisse, W.J., Sener, A., Levy, J. et al. The stimulus-secretion coupling of glucose-induced insulin release. Acta diabet. lat 13, 202–215 (1976). https://doi.org/10.1007/BF02581118
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DOI: https://doi.org/10.1007/BF02581118