Glucose-Induced B-Cell Recruitment and the Expression of Hexokinase Isoenzymes

  • Frans C. Schuit
  • Anick De Vos
  • Karen Moens
  • Erik Quartier
  • Harry Heimberg
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 426)


The balanced release of insulin and glucagon by the endocrine pancreas is an important feature of glucose homeostasis in mammals. Adaptation of hormonal output from the endocrine pancreas to physiological demands is thought to depend on a glucose sensor — also called glucostat — which not only measures the prevailing extracellular glucose concentration but also ensures the signal transduction mechanisms required for appropriate glucagon and insulin release by A-cells and B-cells respectively (1–4). The scope of this paper is restricted to review some recent research concerning glucose sensing in B-cells, neglecting the glucose sensor in glucagon-producing A-cells about which relatively little is known.


Insulin Secretion Insulin Release Glucose Sensor Endocrine Pancreas Balance Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    C.J. Hedeskov, Mechanism of glucose-induced insulin secretion, Physiol. Rev. 60:442–509 (1980).PubMedGoogle Scholar
  2. 2.
    C.B. Wollheim and G.W.G. Sharp, Regulation of insulin release by calcium, Physiol Rev. 61:914–973 (1981).PubMedGoogle Scholar
  3. 3.
    M. Prentki and F.M. Matschinski, Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion, Physiol. Rev. 67:1185–1248 (1987).PubMedGoogle Scholar
  4. 4.
    J.C. Henquin, Cell biology of insulin secretion, In: Joslin’s Diabetes Mellitus, eds. C.R. Kahn, G.C. Weir, Lea & Febiger, Pennsylvania (1994).Google Scholar
  5. 5.
    H.G. Coore and P.J. Randle, Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro, Biochem. J. 93: 66–78 (1964).PubMedGoogle Scholar
  6. 6.
    C. Hellerström, Effects of carbohydrates on the oxygen consumption of isolated pancreatic islets of mice, Endocrinology 81:105–112 (1967).PubMedCrossRefGoogle Scholar
  7. 7.
    D. Pipeleers, P. In’tVeld, E. Maes and M. Van De Winkel, Glucose-induced insulin release depends on functional cooperation between islet cells, Proc. Natl. Acad. Sci. (USA) 79:7322–7325 (1982).CrossRefGoogle Scholar
  8. 8.
    D.F. Steiner, G.I. Bell and H.S. Tager, Chemistry and biosynthesis of pancreatic protein hormones, In: L.J. De Groot, ed. Endocrinology, 2nd Ed., Vol 2 Philadelphia, W.B. Saunders 1263-1289 (1989).Google Scholar
  9. 9.
    F.C. Schuit, P.A. In’tVeld and D.G. Pipeleers, Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells, Proc. Natl. Acad. Sci. (USA) 85:3865–3869 (1989).CrossRefGoogle Scholar
  10. 10.
    D. Salomon and P. Meda, Heterogeneity and contact-dependent regulation of hormone secretion by individual B cells, Exp. Cell Res. 162:507–520 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Hiriart and M.C. Ramirez-Medeles, Functional subpopulations of individual pancreatic B-cells in culture, Endocrinology 128:3193–3198 (1991).PubMedCrossRefGoogle Scholar
  12. 12.
    M. Van De Winkel and D. Pipeleers, Autofluorescence-activated cell sorting of pancreatic islet cells: purification of insulin-containing B-cells according to glucose-induced changes in cellular redox state, Biochem. Biophys. Res. Commun. 114:835–542 (1983).CrossRefGoogle Scholar
  13. 13.
    R. Kiekens, P. In’t Veld, T. Mahler, F. Schuit, M. Van De Winkel and D. Pipeleers, 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 (1992).PubMedCrossRefGoogle Scholar
  14. 14.
    W.J. Malaisse, A. Sener, A. Herchuelz and J.C. Hutton, Insulin release: the fuel hypothesis, Metabolism 28:373–386 (1979).PubMedCrossRefGoogle Scholar
  15. 15.
    M.J. MacDonald, Elusive proximal signals of β-cells for insulin secretion, Diabetes 39:1461–1466 (1990).PubMedCrossRefGoogle Scholar
  16. 16.
    M. Van De Winkel, E. Maes and D. Pipeleers, Islet cell analysis and purification by light scatter and auto-fluorescence, Biochem. Biophys. Res. Commun. 107:525–532 (1982).CrossRefGoogle Scholar
  17. 17.
    H. Heimberg, A. De Vos, A. Vandercammen, E. Van Schaftingen, D. Pipeleers and F. Schuit, Heterogeneity in glucose sensitivity among pancreatic β-cells is correlated to differences in glucose phosphorylation rather than glucose transport, EMBO J. 12:2873–2879 (1993).PubMedGoogle Scholar
  18. 18.
    C.F.H. Van Schravendijk, R. Kiekens and D.G. Pipeleers, Pancreatic β cell heterogeneity in glucose-induced insulin secretion, J. Biol. Chem. 267:21344–21348 (1992).PubMedGoogle Scholar
  19. 19.
    R.H. Unger, Diabetic hyperglycemia: link to impaired glucose transport in pancreatic β cells, Science 251:1200–1205 (1991).PubMedCrossRefGoogle Scholar
  20. 20.
    F. Matschinsky, Y. Liang, P. Kesavan, L. Wang, P. Froguel, G. Velho, D. Cohen, M.A. Permutt, Y. Tanizawa, T.L. Jetton, K. Niswender and M.A. Magnuson, Glucokinase as pancreatic β cell glucose sensor and diabetes gene, J. Clin. Invest. 92:2092–2098 (1993).PubMedCrossRefGoogle Scholar
  21. 21.
    B. Hellman, J. Sehlin and I.B. Täljedal, Evidence for mediated transport of glucose in mammalian pancreatic β-cells, Biochim. Biophys. Acta 241:147–154 (1971).PubMedCrossRefGoogle Scholar
  22. 22.
    F.K. Gorus, W.J. Malaisse and D.G. Pipeleers, Differences in glucose handling by pancreatic A-and B-cells, J. Biol. Chem. 259:1196–1200 (1984).PubMedGoogle Scholar
  23. 23.
    H. Heimberg, A. De Vos, A. Vandercammen, E. Van Schaftingen, D. Pipeleers and F. Schuit, Intercellular differences in glucose phosphorylation can explain the heterogeneity in glucose sensitivity of rat pancreatic β-cells, Diabetologia 36:119 (1993).Google Scholar
  24. 24.
    P.B. Iynedjian, G. Möbius, H.J. Seitz, C.B. Wollheim and A.E. Renold, Tissue-specific expression of glucokinase: Identification of the gene product in liver and pancreatic islets, Proc. Natl. Acad. Sci. USA 83: 1998–2001 (1986).PubMedCrossRefGoogle Scholar
  25. 25.
    T.L. Jetton, Y. Liang, C.C. Pettepher, E.C. Zimmerman, F.G. Cox, K. Horvath, F.M. Matschinsky and M.A. Magnuson, Analysis of upstream glucokinase promoter activity in transgenic mice and identification of glucokinase in rare neuroendocrine cells in the brain and gut, J. Biol Chem. 269:3641–3654 (1994).PubMedGoogle Scholar
  26. 26.
    P.B. Iynedjian, Mammalian glucokinase and its gene, Biochem. J. 293:1–13 (1993).PubMedGoogle Scholar
  27. 27.
    Y. Liang, H. Najafi and F.M. Matschinsky, Glucose regulates glucokinase activity in cultured islets from rat pancreas, J. Biol. Chem. 265:16863–16866 (1990).PubMedGoogle Scholar
  28. 28.
    F. Purrello, M. Buscema, A.M. Rabuazzo, V. Caltabiano, F. Forte, C. Vinci, M. Vetri and R. Vigneri, Glucose modulates glucose transporter affinity, glucokinase activity, and secretory response in rat pancreatic β-cells, Diabetes 42:199–205 (1993).PubMedCrossRefGoogle Scholar
  29. 29.
    M.D. Trus, W.S. Zawalich, P.T. Burch, D.K. Berner, VA. Weill and F.M. Matschinsky, Regulation of glucose metabolism in pancreatic islets, Diabetes 30:911–922 (1981).PubMedCrossRefGoogle Scholar
  30. 30.
    S. Efrat, M. Leiser, Y.J. Wu, D. Fusco-Demane, O.B. Emran, M. Surana, T.L. Jetton, M.A. Magnuson, G. Weir and N. Fleischer, Ribozyme-mediated attenuation of pancreatic β-cell glucokinase expression in transgenic mice results in impaired glucose-induced insulin secretion, Proc. Natl. Acad. Sci. USA 91:2051–2055 (1994).PubMedCrossRefGoogle Scholar
  31. 31.
    N. Vionnet, M. Stoffel, J. Takeda, K. Yasuda, G.I. Bell, H. Zouali, S. Lesage, G. Velho, F. Iris, P. Passa, P. Froguel and D. Cohen, Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus, Nature 356:721–722 (1992).PubMedCrossRefGoogle Scholar
  32. 32.
    G. Velho, P. Froguel, K. Clement, M.E. Pueyo, B. Rakotoambinina, H. Zouali, P. Passa, D. Cohen and J.J. Robert, Primary pancreatic beta-cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young, Lancet 340:444–448 (1992).PubMedCrossRefGoogle Scholar
  33. 33.
    M. Gidh-Jain, J. Takeda, L.Z. Xu, A.J. Lange, N. Vionnet, M. Stoffel, P. Froguel, G. Velho, F. Sun, D. Cohen, P. Patel, Y.M.D. Lo, A.T. Hattersley, H. Luthman, A. Wedell, R. St Charles, R.W. Harrison, I.T. Weber, G.I. Bell and S.J. Pilkis, Glucokinase mutations associated with non-insulin-dependent (type 2) diabetes mellitus have decreased enzyme activity: implications for structure/function relationships, Proc. Natl. Acad. Sci. USA 90:1932–1936 (1993).PubMedCrossRefGoogle Scholar
  34. 34.
    J. Takeda, M. Gidh-Jain, L.Z. Xu, P. Froguel, G. Velho, M. Vaxillaire, D. Cohen, F. Shimada, H. Makino, S. Nishi, M. Stoffel, N. Vionnet, R. St. Charles, R.W. Harrison, I.T. Weber, G.I. Bell and S.J. Pilkis, Structure/ function studies of human β-cell glucokinase, J. Biol. Chem. 268:15200–15204 (1993).PubMedGoogle Scholar
  35. 35.
    E. Van Schaftingen, M. Detheux and M.V. Da Cunha, Short-term control of glucokinase activity: role of a regulatory protein, FASEB J. 8:414–419 (1994).PubMedGoogle Scholar
  36. 36.
    W.J. Malaisse, F. Malaisse-Lagae, D.R. Davies, A. Vandercammen and E. Van Schaftingen, Regulation of glucokinase by a fructose-1-phosphate sensitive protein in pancreatic islets, Eur. J. Biochem. 190: 539–545 (1990).PubMedCrossRefGoogle Scholar
  37. 37.
    M-H. Giroix, A. Sener, D.G. Pipeleers and W.J. Malaisse, Hexose metabolism in pancreatic islets, Biochem. J. 223:447–453 (1984).PubMedGoogle Scholar
  38. 38.
    U. Vischer, B. Blondel, C.B. Wollheim, W Höppner, H.J. Seitz and P.B. Iynedjian, Hexokinase isoenzymes of RIN-m5F insulinoma cells, Biochem. J. 241:249–255 (1987).PubMedGoogle Scholar
  39. 39.
    I. Swenne, Effects if ageing on the regenerative capacity of the pancreatic B-cell of the rat, Diabetes 32:14–19 (1983).PubMedCrossRefGoogle Scholar
  40. 40.
    P.N. Epstein, A.C. Boschero, I. Atwater, X. Cai and P.A. Overbeek, Expression of yeast hexokinase in pancreatic β cells of transgenic mice reduces blood glucose, enhances insulin secretion, and decreases diabetes, Proc. Natl. Acad. Sci. USA 89:12038–12042 (1992).PubMedCrossRefGoogle Scholar
  41. 41.
    M.E. Voss-McCowan, B. Xu and P.N. Epstein, Insulin synthesis, secretory competence, and glucose utilization are sensitized by transgenic yeast hexokinase, J. Biol Chem. 269:15814–15818 (1994).PubMedGoogle Scholar
  42. 42.
    M.S. German, Glucose sensing in pancreatic islet beta cells: The key role of glucokinase and the glycolytic intermediates, Proc. Natl. Acad. Sci. USA 90:1781–1785 (1993).PubMedCrossRefGoogle Scholar
  43. 43.
    M. Asafari, D. Janjic, P. Meda, G. Li, P.A. Halban, C.B. Wollheim, Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines, Endocrinology 130:167–178 (1992).CrossRefGoogle Scholar
  44. 44.
    S. Efrat, M. Leiser, M. Surana, M. Tal, D. Fusco-Demane, N. Fleischer, Murine insulinoma cell line with normal glucose-regulated insulin secretion, Diabetes 42:901–907 (1993).PubMedCrossRefGoogle Scholar
  45. 45.
    H. Ishihara, T. Asano, K. Tsukuda, H. Katagiri, K. Inukai, M. Anai, M. Kikuchi, Y. Yazaki, J.I. Miyazaki and Y. Oka, Pancreatic beta cell line MIN6 exhibits characteristics of glucose metabolism and glucose-stimulated insulin secretion similar to those of normal islets, Diabetologia 36:1139–1145 (1993).PubMedCrossRefGoogle Scholar
  46. 46.
    H. Ishihara, T. Asano, K. Tsukuda, H. Katagiri, K. Inukai, M. Anai, M. Kikuchi, Y. Yazaki, J.I. Miyazaki and Y. Oka, Overexpression of hexokinase I but not GLUT1 glucose transporter alters concentration dependence of glucose-stimulated insulin secretion in pancreatic β-cell line MIN6, J. Biol. Chem. 269:3081–3087 (1994).PubMedGoogle Scholar
  47. 47.
    C.B. Newgard, Cellular engineering and gene therapy strategies for insulin replacement in diabetes, Diabetes 43:341–350 (1994).PubMedCrossRefGoogle Scholar
  48. 48.
    S.D. Hughes, C. Quaade, J.H. Johnson, S. Ferber and C.B. Newgard, Transfection of AtT-20ins cells with GLUT-2 but not GLUT-1 confers glucose-stimulated insulin secretion, J. Biol. Chem. 268:15205–15212 (1993).PubMedGoogle Scholar
  49. 49.
    S. Ferber, H. BeltrandelRio, J. Johnson, R.J. Noel, L.E. Cassidy, S. Clark, T.C. Becker, S. Hughes and C.B. Newgard, GLUT-2 gene transfer into insulinoma cells confers both low and high affinity glucose-stimulated insulin release, J. Biol. Chem. 269:11523–11529 (1994).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Frans C. Schuit
    • 1
  • Anick De Vos
    • 1
  • Karen Moens
    • 1
  • Erik Quartier
    • 1
  • Harry Heimberg
    • 1
  1. 1.Department of Biochemistry, Diabetes Research CenterVrije Universiteit BrusselBrusselsBelgium

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