Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The mechanism of insulin secretion

  • 601 Accesses

  • 35 Citations


  1. 1.

    von Mering J, Minkowski O (1889) Diabetes mellitus nach Pankreasexstirpation. Arch exp Pathol Pharmakol 26: 371–387

  2. 2.

    Minkowski O (1893) Untersuchungen über den Diabetes mellitus nach Exstirpation des Pankreas. Arch Exp Pathol Pharmakol 31: 85–103

  3. 3.

    Moskalewski S (1965) Isolation and culture of the islets of Langerhans of the guinea pig. Gen Comp Endocrinol 5: 342–353

  4. 4.

    Howell SL, Taylor KW (1966) Effects of glucose on incorporation of (3H)leucine into insulin in isolated islets of Langerhans. Biochim Biophys Acta 130: 519–521

  5. 5.

    Lacy PE, Kostianovsky MK (1967) Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16:35–39

  6. 6.

    Howell SL, Taylor KW (1968) Potassium ions and the regulation of insulin secretion by isolated islets of Langerhans incubated in vitro. Biochem J 108: 17–24

  7. 7.

    Hellerström C (1964) A method for the microdissection of intact pancreatic islets of mammals. Acta Endocrinol 45: 122–132

  8. 8.

    Howell SL (1982) The insulin storage granule. In: Poisner AM, Trifaro JM (eds) The secretory granule. Elsevier Medical, Amsterdam, pp 155–172

  9. 9.

    Humbel RE, Bossha RD, Zahn H (1972) Chemistry of insulin. In: Steiner DF, Freinkel N (eds) Handbook of physiology, section 7, voll. American Physiological Society Washington, DC, pp 111–132

  10. 10.

    Steiner DF, Kemmler W, Tager HS, Rubenstein A (1974) Molecular events taking place during the intracellular transport of exportable proteins. Cytopharmacology of Secretion 2: 195–205

  11. 11.

    Howell SL, Tyhurst M, Duvefelt H, Andersson A, Hellerström C (1978) Role of zinc and calcium in the formation and storage of insulin in the pancreatic B cell. Cell Tissue Res 188: 107–118

  12. 12.

    Hahn HJ, Gylfe E, Hellman B (1979) Glucose-dependent effect of methylxanthines on the 45Ca2+ distribution in pancreatic B cells. FEBS Lett 103: 348–351

  13. 13.

    Wollheim CB, Sharp GWG (1981) Regulation of insulin release by calcium. Physiol Rev 61: 914–973

  14. 14.

    Cegrell L (1968) The occurrence of biogenic amines in the mammalian endocrine pancreas. Acta Physiol Scand: Suppl 314

  15. 15.

    Dean PM (1973) Ultrastructural morphometry of the pancreatic B cell. Diabetologia 9: 115–119

  16. 16.

    Howell SL, Tyhurst M (1977) Distribution of anionic sites on the surface of B cell granule and plasma membranes: a study using cationic ferritin. J Cell Sci 27: 289–301

  17. 17.

    Brown EM, Pazoles CJ, Kreutz CE, Aurbach GD, Pollard HB (1978) Role of anions in parathyroid hormone release from dispersed bovine parathyroid cells. Proc Natl Acad Sci USA 75: 876–880

  18. 18.

    Orci L, Malaisse WJ (1980) Single and chain release of insulin secretory granules is related to anionic transport at exocytotic sites. Diabetes 29: 943–944

  19. 19.

    Yaseen MA, Smith JE, Doolabh K, Howell SL (1983) Insulin secretion by exocytosis from permeabilized islets of Langerhans. Diabetologia 25: 205–206 (Abstract)

  20. 20.

    Dean PM (1975) Exocytosis modelling: an electrostatic function for calcium in stimulus-secretion coupling. J Theor Biol 54: 289–308

  21. 21.

    Burridge K, Phillips JH (1975) Association of actin and myosin with secretory granule membranes. Nature (Lond) 254:526–529

  22. 22.

    Hutton JC, Peshavaria M (1982) Proton-translocating Mg2+ dependent ATPase activity in insulin secretory granules. Biochem J 204: 161–170

  23. 23.

    Tanaka K (1980) Scanning electron microscopy of intracellular structures. Int Rev Cytol 68: 97–125

  24. 24.

    Howell SL, Tyhurst M (1982) Microtubules, microfilaments and insulin secretion. Diabetologia 22: 301–308

  25. 25.

    Lacy PE, Howell SL, Young DA, Fink CJ (1968) A new hypothesis of insulin secretion. Nature (Lond) 219: 1177–1179

  26. 26.

    Lacy PE, Walker MM, Fink CJ (1972) Perifusion of isolated rat islets in vitro. Participation of the microtubular system in the phasic mechanism of insulin release. Diabetes 21: 987–998

  27. 27.

    Van Obberghen E, Somers G, Devis G, Ravazzola M, Malaisse-Lagae F, Orci L, Malaisse WJ (1975) Dynamics of insulin release of the microtubular-microfilamentous system. VI. Effects of D2O. Endocrinology 95: 1518–1528

  28. 28.

    Malaisse WJ, Malaisse-Lagae F, Van Obherghen E, Somers G, Devis G, Ravazzola M, Orci L (1975) Role of microtubules in the phasic pattern of insulin release. Ann NY Acad Sci 253: 630–652

  29. 29.

    Howell SL, Hii CST, Shaikh S, Tyhurst M (1982) Effects of taxol and nocodazole on insulin secretion from isolated rat islets of Langerhans. Biosci Rep 2: 795–801

  30. 30.

    Montague W, Howell SL, Green IC (1975) Insulin release and the microtubular system of the islets of Langerhans. Biochem J 148: 237–243

  31. 31.

    Sloboda RD, Rudolph SA, Rosenbaum JL, Greengard P (1975) Cyclic AMP-dependent endogenous phosphorylation of a microtubule-associated protein. Proc Natl Acad Sci (USA) 72: 177–181

  32. 32.

    Colca JR, Brooks CL, Landt M, McDaniel ML (1983) Correlation of Ca2+ and calmodulin-dependent protein kinase activity with secretion of insulin from islets of Langerhans. Biochem J 212: 819–827

  33. 33.

    Orci L, Gabbay KH, Malaisse WJ (1972) Pancreatic B cell web: its possible role in insulin secretion. Science 175: 1128–1130

  34. 34.

    Howell SL, Tyhurst M (1980) Regulation of actin polymerization in rat islets of Langerhans. Biochem J 192: 381–383

  35. 35.

    Swanston-Flatt SK, Carlsson L, Gylfe E (1980) Actin filament formation in pancreatic B cells during glucose stimulation of insulin secretion. FEBS Lett 117: 299–302

  36. 36.

    Mimura N, Asano A (1979) Ca2+ sensitive gelation of actin filaments by a new protein factor. Nature (Lond) 282: 44–47

  37. 37.

    Yin HL, Stossl TP (1979) Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein. Nature 281: 583–586

  38. 38.

    Hasegawa T, Takahashi S, Hayashi H, Hatano S (1980) Fragmin: a calcium ion sensitive regulatory factor on the formation of actin filaments. Biochemistry 19: 2677–2683

  39. 39.

    Bretscher A, Weber K (1980) Villin is a major protein of the microvillous cytoskeleton which binds both G and F actin in a calcium-dependent anner. Cell 20: 839–847

  40. 40.

    Glenny JR, Glenney P, Weber K (1982) F-actin binding and crosslinking properties of porcine brain fodrin, a spectrin related molecule. J Biol Chem 257: 9781–9787

  41. 41.

    Sobue K, Morimoto Y, Fujita M, Kakiuchi S (1981) Purification of a calmodulin binding protein from chicken gizzard that reacts with F-actin. Proc Natl Acad Sci USA 78: 5652–5655

  42. 42.

    McDonald MJ, Kowluru A (1982) Calcium activated factors in pancreatic islets that inhibit actin polymerization. Arch Biochem Biophys 219: 459–462

  43. 43.

    Ostlund RE, Leung JT, Kipnis DM (1978) Myosins of secretory tissues. J Cell Biol 77: 827–836

  44. 44.

    Harrison DE, Ashcroft SJH (1982) Phosphorylation — dephosphorylation mechanisms and insulin secretion: Ca2+ dependent enzymes of protein and phospholipid metabolism of rat islets of Langerhans. Diabetologia 23: 172–173

  45. 45.

    McDonald MJ, Kowluru A (1982) Calcium-calmodulin dependent myosin phosphorylation by pancreatic islets. Diabetes 31: 566–570

  46. 46.

    Penn EJ, Brocklehurst KW, Sopwith AM, Hales CN, Hutton JC (1982) Ca2+-calmodulin dependent myosin light chain phosphorylating activity in insulin secreting tissues. FEBS Lett 139: 4–8

  47. 47.

    Suprenant KA, Dentier WL (1982) Association between endocrine pancreatic secretory granules and in vitro assembled microtubules is dependent upon microtubule-associated proteins. J Cell Biol 93: 164–174

  48. 48.

    Howell SL, Tyhurst M (1979) Interaction between insulin storage granules and F-actin in vitro. Biochem J 178: 367–371

  49. 49.

    Howell SL, Tyhurst M (1982) Actomyosin interactions with insulin storage granules in vitro. Biochem J 206: 157–160

  50. 50.

    Henquin JC (1981) Effects of trifluoperazine and pimozide on stimulus-secretion coupling in pancreatic B cells. Biochem J 196: 771–780

  51. 51.

    Gagliardino JJ, Harrison DE, Christie MR, Gagliardino EE, Ashcroft SJH (1980) Evidence for the participation of calmodulin in stimulus-secretion coupling in the pancreatic B cell. Biochem J 192: 919–927

  52. 52.

    Christie MR, Ashcroft SJH (1984) Cyclic-AMP dependent protein phosphorylation and insulin secretion in intact islets of Langerhans. Biochem J (in press) 218: 87–99

  53. 53.

    Schubart UK (1982) Regulation of protein phosphorylation in hamster insulinoma cells. J Biol Chem 257: 12231–12238

  54. 54.

    Sheetz MP, Spudich JA (1983) Movement of myosin-coated fluorescent beads on actin cables in vitro. Nature 303: 31–35

  55. 55.

    Griffith LM, Pollard TD (1978) Evidence for actin filament-microtubule interactions mediated by microtubule-associated proteins. J Cell Biol 78: 958–965

  56. 56.

    Nishada E, Kuwaki T, Sakai H (1983) Phosphorylation of microtubule associated proteins and pH of the medium control interaction between MAPs and actin filaments. J Biochem (Tokyo) 90: 575–578

  57. 57.

    Sattilaro RF, Dentier WL, Le Cluyse EL (1981) Microtubule associated proteins and the organization of actin filaments in vitro. J Cell Biol 90: 467–473

  58. 58.

    Lacy PE, Lacy ET, Finke EH, Yasunami Y (1982) An improved method for the isolation of islets from the beef pancreas. Diabetes 31 (Suppl 4): 109–111

  59. 59.

    van der Winkel M, Maes E, Pipeleers D (1982) Islet cell analysis and purification by light scattering and autofluorescence. Biochem Biophys Res Commun 107: 525–532

  60. 60.

    van der Winkel M, Smets G, Gepts W, Pipeleers D (1982) Islet cell surface antibodies from insulin dependent diabetics binding specifically to pancreatic B cells. J Clin Invest 70: 41–49

Download references

Author information

Additional information

This paper is based on the text of the 18th Minkowski Lecture of the European Association for the Study of Diabetes, delivered at its meeting in Oslo, September 1983

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Howell, S.L. The mechanism of insulin secretion. Diabetologia 26, 319–327 (1984). https://doi.org/10.1007/BF00266030

Download citation


  • Public Health
  • Internal Medicine
  • Human Physiology
  • Metabolic Disease
  • Insulin Secretion