Reconstructing Islet Function In Vitro
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Throughout the day, insulin secretion and biosynthesis result from the activity of numerous β-cells which function in coordination. Until recently, it has been implicitly assumed that all these cells are alike, i.e. that they secrete synchronously and at the same rate under various conditions. However, several lines of evidence now show that the actual situation is more complex. Thus, in situ, individual β-cells show variable amounts of secretory granules and rough endoplasmic reticulum, different thresholds for glucose-induced electrical activity[2,3] and a variable ability to biosynthesize insulin. Furthermore, the β-cells located at the periphery of the islets differ from those located in the center of the microorgan with regard to nucleus size[5,6], incorporation of [3H]-thymidine, number of gap junctions, extent of dye coupling, electrical activity[10,11], and ability to secrete insulin. In vitro studies have also revealed marked differences between individual β-cells with respect to insulin release[13–17], electrical activity and Ca2+ changes during stimulation[19,20] as well as with respect to protein biosynthesis and glucose-activated metabolic redox changes[21–23]. This wide heterogeneity, which is reviewed in the first part of this chapter, raises the question of how β-cells achieve the proper coordination which is necessary to ensure appropriate insulin biosynthesis and secretion under continously changing physiological conditions.
KeywordsInsulin Secretion Pancreatic Islet Insulin Release Plaque Assay Insulin Gene
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- 2.Mathews, E.K., and Dean, P.M., 1970, Electrical activity in islet cells, In: “Structure and Metabolism of Pancreatic Islets,” S. Falkmer, B. Hellman and I.-B. Taljedal, eds., Cambridge University Press, Cambridge, pp. 305–313.Google Scholar
- 3.Beigelman, P., Ribalet, B., and Atwater, I., 1977, Electrical activity of mouse pancreatic beta-cells. II. Effects of glucose and arginine, J. Physiol. (Paris) 73:201–217.Google Scholar
- 21.Pipeleers, D., and Van de Winkel, M., 1989, Cellular endogenous fluorescence: a basis for preparing populations of functionally homogeneous cells, in: “Cell Structure and Function by Microspectrofluorometry,” E. Kohen and J.G. Hirschberg, eds., Academic, San Diego, CA, pp. 391–404.Google Scholar
- 22.Kiekens, R., In’t Veld, P., Mahler, T., Schuit, F., Van De Winkel, M., and Pipeleers, D., 1992, Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity, J. Clin. Invest. 89:117–125.PubMedCrossRefGoogle Scholar
- 23.Van Schravendijik, C.F.H., Kiekens, R., and Pipeleers, D.G., 1992, Pancreatic cell heterogeneity in glucose-induced insulin secretion, J. Biol. Chem. 267:21344–21348.Google Scholar
- 25.Pipeleers, D., Hooghe-Peters, E., Maes, E., Schuit, F., Van De Winkel, M., and Van Schravendijk, C., 1982a, Reconstructing the pancreatic islet and its glucose-induced insulin release, Diabetologia 23:191 (abstract).Google Scholar
- 34.Meda, P., Chanson, M., Pepper, M., Giordano, E., Bosco, D., Traub, O., Willecke, K., El Aoumari, A., Gros, D., Beyer, E., Orci, L., and Spray, D.C., 1991, In vivo modulation of connexin 43 gene expression and junctional coupling of pancreatic B-cells, Exp. Cell Res. 192:469–480.PubMedCrossRefGoogle Scholar
- 42.Appel, M.C., O’Neill, J.J., and Meda, P., 1988, Effects of glucose on islet gap junctional communication, Diabetes 37, suppl 1, 47A (abstract).Google Scholar
- 44.44.Ullrich, S., Vozzi, C., and Meda, P., 1993, Connexins of insulin-secreting cells: Quantification of mRNA by polymerase chain reaction, Diabetologia 36 (Suppl 1): A5 (abstract).Google Scholar
- 45.Vozzi, C., Ullrich, S., Bosco, D., Dupont, E., and Meda, P., 1994, Glucose-unresponsive insulin-producing cells show defects in gap junction coupling and improved secretion after Cx43 transfection. Acta Anat. 149:162 (abstract).Google Scholar