Microscopic Anatomy of the Human Islet of Langerhans

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 654)


Human islets of Langerhans are complex micro-organs responsible for maintaining glucose homeostasis. Islets contain five different endocrine cell types, which react to changes in plasma nutrient levels with the release of a carefully balanced mixture of islet hormones into the portal vein. Each endocrine cell type is characterized by its own typical secretory granule morphology, different peptide hormone content, and specific endocrine, paracrine, and neuronal interactions. During development, a cascade of transcription factors determines the formation of the endocrine pancreas and its constituting islet cell types. Differences in ontogeny between the ventrally derived head section and the dorsally derived head, body, and tail section are responsible for differences in innervation, blood supply, and endocrine composition. Islet cells show a close topographical relationship to the islet vasculature, and are supplied with a five to tenfold higher blood flow than the exocrine compartment. Islet microanatomy is disturbed in patients with type 1 diabetes, with a marked reduction in β-cell content and the presence of inflammatory infiltrates. Histopathological lesions in type 2 diabetes are less pathognomonic with a more limited reduction in β-cell content and occasional deposition of amyloid in the islet interstitial space.


Pathology Type 1 diabetes Type 2 diabetes Morphology Anatomy Insulitis Amyloid β-cell α-cell δ-cell PP cell Autoimmunity Innervation Vasculature Non-endocrine cells 



PV and MM are supported by grants from the FWO-Vlaanderen (G0289088) and the JDRF (26-2008-896). Ms Jenny Mertens is acknowledged for secretarial assistance and Dr. Frans Gorus for critical reading of the manuscript.


  1. 1.
    Ogilvie RF. A quantitative estimation of the pancreatic islet tissue. Quart J Med 1937; 6:287–300.Google Scholar
  2. 2.
    Volk BW, Wellman KF. Historical review. In: Volk BW, Arquilla ER, editors. The diabetic pancreas. New York: Plenum; 1985: p. 1–16.Google Scholar
  3. 3.
    Hellman B, Hellerström C. Histology and histophysiology of the islets of Langerhans in man. In Pfeiffer EF, editor. Handbook of diabetes mellitus. Munich: Lehmanns, V; 1969: p. 90–118.Google Scholar
  4. 4.
    Goldstein MB, Davis EA. The three dimensional architecture of the islets of Langerhans. Acta Anat 1968;71:161–71.PubMedGoogle Scholar
  5. 5.
    Hughes SJ, Clark A, McShane P, Contractor HH, Gray DW, Johnson PR. Characterisation of collagen VI within the islet exocrine interface of the human pancreas: implications for clinical islet isolation? Transplantation 2006;81:423–6.PubMedGoogle Scholar
  6. 6.
    Smith PH. Structural modification of Schwann cells in the pancreatic islet of the dog. Am J Anat 1975;144:513–7.PubMedGoogle Scholar
  7. 7.
    Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes, Obesity and Metabolism 2008;10 Suppl 4: 32–42.PubMedGoogle Scholar
  8. 8.
    Pictet R, Rutter WJ. Development of the embryonic endocrine pancreas. In: Steiner DF, Freinkel N, editors. Handbook of Physiology. Section 7: Endocrinology. Vol. 1: Endocrine pancreas. Baltimore: Williams & Wilkins; 1972. p. 25–66.Google Scholar
  9. 9.
    Edlund H. Pancreatic organogenesis-developmental mechanisms and implications for therapy. Nature Rev Gen 2002;3:524–32.Google Scholar
  10. 10.
    Bencosme SA, Liepa E. Regional differences of the pancreatic islet. Endocrinology 1955;57: 588–93.PubMedGoogle Scholar
  11. 11.
    Orci L, Malaisse-Lagae F, Baetens D, Perrelet A. Pancreatic-polypeptide-rich regions in human pancreas. Lancet 1978;ii:1200–1.Google Scholar
  12. 12.
    Murtaugh LC. Pancreas and beta-cell development: from the actual to the possible. Development 2007; 134:427–38.PubMedGoogle Scholar
  13. 13.
    Stefan Y, Grasso S, Perrelet A, Orci L. A quantitative immunofluorescent study of the endocrine cell populations in the developing human pancreas. Diabetes 1983;32:293–301.PubMedGoogle Scholar
  14. 14.
    Xu X, D Hoker J, Stangé G, Bonné S, De Leu N, Xiao X, Van De Casteele M, Meelitzer G, Ling Z, Pipeleers D, Bouwens L, Scharfmann R, Gradwohl G, Heimberg H. Beta cells can be generated from endogeneous progenitors in injured adult mouse pancreas. Cell 2008;132:197–207.PubMedGoogle Scholar
  15. 15.
    Kassem SA, Ariel I, Thornton PS, Scheimberg I, Glaser B. Beta cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy. Diabetes 2000;49:1325–33.PubMedGoogle Scholar
  16. 16.
    Meier JJ, Butler AE, Saisho Y, Monchamp T, Galasso R, Bhushan A, Rizza RA, Butler PC. Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans. Diabetes 2008;57:1584–94.PubMedGoogle Scholar
  17. 17.
    Bouwens L, Lu WG, De Krijger R. Proliferation and differentiation in the human fetal pancreas. Diabetologia 1997;40:398–404.PubMedGoogle Scholar
  18. 18.
    Rahier J, Wallon J, Henquin JC. Cell populations in the endocrine pancreas of human neonates and infants. Diabetologia 1981;20:540–6.PubMedGoogle Scholar
  19. 19.
    Orci L, Stefan Y, Malaisse-Lagae F, Perrelet A. Instability of pancreatic endocrine cell population throughout life. Lancet 1979;1:615–6.PubMedGoogle Scholar
  20. 20.
    Clark A, Grant AM. Quantitative morphology of endocrine cells in human fetal pancreas. Diabetologia 1983;25:31–5.PubMedGoogle Scholar
  21. 21.
    Like AA, Orci L. Embryogenesis of the human fetal pancreatic islets: a light and electron microscopic study. Diabetes 1972;21:511–34.PubMedGoogle Scholar
  22. 22.
    Lane MA. The cytological characteristics of the areas of Langerhans. Am J Anat 1907; 409–22.Google Scholar
  23. 23.
    Bloom W. A new type of granular cell in the islets of Langerhans of man. Anat Record 1931;49: 363–71.Google Scholar
  24. 24.
    Kimmel JR, Pollock HG, Hazelwood RL. A new pancreatic polypeptide. Fed Proc (USA) 1971; 30:1318 (abstr).Google Scholar
  25. 25.
    Wierup N, Svensson H, Mulder H, Sundler F. The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Reg Peptides 2002;107:63–9.Google Scholar
  26. 26.
    Murlin JR, Clough HG, Gibbs CB, Stokes AM. Aqueous extracts of pancreas. I. Influence on the carbohydrate metabolism of depancreatized animals. J Biol Chem 1923;56:253.Google Scholar
  27. 27.
    Bell GI, Santere RF, Mullenbach GT. Hamster preproglucagon contains the sequence of glucagons and two related peptides. Nature 1983;302:716–8.PubMedGoogle Scholar
  28. 28.
    Vaillant CR, Lund PK. Distribution of glucagons-like peptide I in canine and feline pancreas and gastrointestinal tract. Histochem Cytochem 1986;34:1117–21.Google Scholar
  29. 29.
    Deconinck JF, Potvliege PR, Gepts W. The ultrastructure of the human pancreatic islets. I. The islets of adults. Diabetologia 1971;7:266–82.PubMedGoogle Scholar
  30. 30.
    Baum J, Simmons BE, Unger RH, Madison LL, Localization of glucagon in the A-cells in the pancreatic islet by immunofluorescence. Diabetes 1962:11;371–4.PubMedGoogle Scholar
  31. 31.
    Stefan Y, Orci L, Malaisse-Lagae F, Perrelet A, Patel Y, Unger RH. Quantitation of endocrine cell content in the pancreas of non-diabetic and diabetic humans. Diabetes 1982;31:694–700.PubMedGoogle Scholar
  32. 32.
    Rahier J, Goebbels RM, Henquin JC. Cellular composition of the human diabetic pancreas. Diabetologia 1983;24:366–71.PubMedGoogle Scholar
  33. 33.
    Brissova M, Fowler MJ, Nicholson WE, Chu A, Hirshberg B, Harlan DM, Powers AC. Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. J Histochem Cytochem 2005;53:1087–97.PubMedGoogle Scholar
  34. 34.
    Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren PO, Caicedo A. The unique cytoarchitecture of human pancreatic islets has implications for islet function. Proc Natl Acad Sci USA 2006;103:2334–9.PubMedGoogle Scholar
  35. 35.
    Banting FG, Best CH. The internal secretion of the pancreas. J Lab Clin Med 1922; 7:465–80.Google Scholar
  36. 36.
    Bliss M. The discovery of insulin. University of Chicago Press, 1982.Google Scholar
  37. 37.
    Orci L. The insulin cell: its cellular environment and how it processes (pro)insulin. Diabetes Metab Rev 1986; 2:71–106.PubMedGoogle Scholar
  38. 38.
    Johnson KH, O Brien TD, Hayden DW, Jordan K, Ghobrial HKG, Mahoney WC, Westermark P. Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. Am J. Pathol 1988;130:1–8.PubMedGoogle Scholar
  39. 39.
    Lacy PE. Electron microscopic and fluorescent antibody studies on islets of Langerhans. Exp Cell Res 1959;7:296–308.Google Scholar
  40. 40.
    Maske H. Interaction between insulin and zinc in the islets of Langerhans. Diabetes 1957;6:335–341.PubMedGoogle Scholar
  41. 41.
    Olofsson CS, Göpel SO, Barg S, Galvanovskis J, Ma X, Salehi A, Rorsman P, Eliasson L. Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic beta cells. Pflugers Arch 2002;444:43–51.PubMedGoogle Scholar
  42. 42.
    Dean PM, Ultrastructural morphometry of the pancreatic beta cell. Diabetologia 1973;9:115–119.PubMedGoogle Scholar
  43. 43.
    Eliasson L, Abdulkader F, Braun M, Galvanovski J, Hoppa MB, Rorsman P. Novel aspects of the molecular mechanisms controlling insulin secretion. J Physiol 2008;586:3313–24.PubMedGoogle Scholar
  44. 44.
    Eiden LE. Is chromogranin-A a prohormone? Nature 1987;325:301.PubMedGoogle Scholar
  45. 45.
    Hutton JC, Peshavaria M, Johnston CF, Ravazzola M, Orci L. Immunolocalization of betagranin: a chromogranin A-related protein of the pancreatic B-cell. Endocrinology 1988;122:1014–20.PubMedGoogle Scholar
  46. 46.
    Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, Rewers M, Eisenbarth GS, Jensen J, Davidson HW, Hutton JC. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci (USA) 2007;104:17040–5.Google Scholar
  47. 47.
    Lan MS, Wasserfall C, Maclaren NK, Notkins L. IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus. Proc Natl Acad Sci (USA) 1996;93:6367–70.Google Scholar
  48. 48.
    Baekkeskov S, Aanstoor HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, De Camilli P. Identification of the 64 k autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 1990;347:151–6.PubMedGoogle Scholar
  49. 49.
    Schuit F, In t Veld PA, Pipeleers DG. Glucose recruits pancreatic B-cells to proinsulin biosynthesis. Proc Natl Acad Sci USA 1988;85:3865–9.PubMedGoogle Scholar
  50. 50.
    Ehrie MG, Swartz FJ. Diploid, tetraploid and octaploid beta cells in the islets of Langerhans of the normal human pancreas. Diabetes 1974;23:583–8.PubMedGoogle Scholar
  51. 51.
    Cnop M, Grupping A, Hoorens A, Bouwens L, Pipeleers-Marichal M, Pipeleers D. Endocystosis of low density lipoprotein by human pancreatic B-cells and uptake in lipid-storing vesicles which accumulate with age. Amer J Pathol 2000;156:237–44.Google Scholar
  52. 52.
    Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973;179:77–9.PubMedGoogle Scholar
  53. 53.
    Luft R, Efendic S, Hökfelt T, Johansson O, Azimura A. Immunohistochemical evidence for the localization of somatostatin-like immunoreactivity in a cell population of the pancreatic islets. Med Biol 1974;52:428–30.PubMedGoogle Scholar
  54. 54.
    Bloom SR, Polak JM. Somatostatin. Br Med J 1987;295:288–9.Google Scholar
  55. 55.
    Grube D, Bohn R. The microanatomy of human islets of Langerhans with special reference to somatostatin (D-) cells. Arch Histol Jap 1983;46:327–53.PubMedGoogle Scholar
  56. 56.
    Larsson LI, Sundler F, Hakansson R, Pollock HG, Kimmel JR. Localization of APP, a postulated new hormone to a pancreatic endocrine cell type. Histochemistry 1974;42:377–82.PubMedGoogle Scholar
  57. 57.
    Watanabe T, Yaegashi H, Koizumi M, Toyota T, Takahashi T. Changing distribution of islets in the developing human pancreas: a computer-assisted three-dimensional reconstruction study. Pancreas 1999;18:349–54.PubMedGoogle Scholar
  58. 58.
    Wittingen J, Frey CF. Islet concentration in the head, body, tail and uncinate process of the pancreas. Ann Surg 1974;179:412–4.PubMedGoogle Scholar
  59. 59.
    Saito K, Takahashi T, Yagginuma B, Iwama N. Morphometrical analysis on topographical difference in size distribution, number and volume of islets in the human pancreas. Tohoku J exp Med 1978;124:177–86.PubMedGoogle Scholar
  60. 60.
    Orci L, Baetens D, Ravazzola M, Stefan Y, Malaisse-Lagae F. Pancreatic polypeptide and glucagon: non-random distribution in pancreatic islets. Life Sci 1976;19:1811–5.PubMedGoogle Scholar
  61. 61.
    Klimstra DS, Hruban RH, Pitman MR. In: Histology for Pathologists, 3rd ed. Stacey E Mills, editor. Lippincott, Wiliams & Wilkins 2007.Google Scholar
  62. 62.
    Bouwens L, Pipeleers DG. Extra-insular beta cells associated with ductules are frequent in adult human pancreas. Diabetologia 1998;41:452–9.PubMedGoogle Scholar
  63. 63.
    Dor Y, Brown J, Martinez OI, Melton D. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004;429:41–6.PubMedGoogle Scholar
  64. 64.
    Gomori G. A differential stain for cell types in the pancreatic islets; Am J Pathol 1939;15:497–9.PubMedGoogle Scholar
  65. 65.
    Grimelius L, Strand A. Ultrastructural studies of the argyrophil reaction in alpha1 cells in human pancreatic islets. Virchows Arch A Pathol Anat Histol 1974;364:129–35.PubMedGoogle Scholar
  66. 66.
    Hellerström C, Hellman B. Some aspects of silver impregnation of the islets of Langerhans in the rat, Acta endocrinol (Copenh.) 1960;35:518–32.Google Scholar
  67. 67.
    de Koning EJ, van den Brand JJ, Mott VL, Chargé SB, Hansen BC, Bodkin NL, Moris JF, Clark A. Macrophages and pancreatic islet amyloidosis. Amyloid 1998;5:247–54.PubMedGoogle Scholar
  68. 68.
    O Morchoe CC. Lymphatic system of the pancreas. Micros Res Tech 1997;37:456–77.Google Scholar
  69. 69.
    Jansson L, Carlsson PO. Graft vascular function after transplantation of pancreatic islets. Diabetologia 2002;45:749–63.PubMedGoogle Scholar
  70. 70.
    Ballian N. Islet vasculature as a regulator of endocrine pancreas function. World J Surg 2007;31:705–14.PubMedGoogle Scholar
  71. 71.
    Zanone MM, Favaro E, Camussi G. From endothelial to beta cells: insights into pancreatic islet microendothelium. Curr Diabetes Rev 2008;4:1–9.PubMedGoogle Scholar
  72. 72.
    Zanone MM, Favaro E, Doublier S, Lozanoska-Ochser B, Deregibus MC, Greening J, Huang GC, Klein N, Cavallo Perin P, Peakman M, Camussi G. Expression of nephrin by human pancreatic islet endothelial cells. Diabetologia 2005;48:1789–97.PubMedGoogle Scholar
  73. 73.
    Henderson JR, Moss MC. A morphometric study of the endocrine and exocrine capillaries of the pancreas. Q J Exp. Physiol 1985;70:347–56.PubMedGoogle Scholar
  74. 74.
    Lammert E, Gu G, McLaughlin M, Brown D, Brekken R, Murtaugh LC, Gerber HP, Ferrara N, Melton DA. Role of VEGF-A in vascularization of pancreatic islets. Current Biology 2003;13:1070–4.PubMedGoogle Scholar
  75. 75.
    Bonner-Weir S. Morphological evidence for pancreatic polarity of beta cell within islets of Langerhans. Diabetes 1988;37:616–21.PubMedGoogle Scholar
  76. 76.
    Virtanen I, Banerjee M, Palgi J, Korsgren O, Lukinius A, Thornell LE, Kikkawa Y, Sekiguchi K, Hukkanen M, Konttinen YT, Otonkoski T. Blood vessels of human islets of Langerhans are surrounded by a double basement membrane. Diabetologia 2008;51:1181–91.PubMedGoogle Scholar
  77. 77.
    Koma Y, Furuno T, Hagiyama M, Hamaquchi K, Nakanishi M, Masuda M, Hirota S, Yokozaki H, Ito A. Cell adhesion molecule 1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions. Gastroenterology 2008;134:1544–54.PubMedGoogle Scholar
  78. 78.
    Ahrén B. Regulation of insulin secretion by nerves and neuropeptides. Ann Acad Med Singapore 1999;28:99–104.PubMedGoogle Scholar
  79. 79.
    Tsui H, Winer S, Chan Y, Truong D, Tang L, Yantha J, Paltser G, Dosch HM. Islet glia, neurons, and beta cells. Ann NY Acad Sci 2008;1150–32–42.PubMedGoogle Scholar
  80. 80.
    Gepts W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 1965;14:619–33.PubMedGoogle Scholar
  81. 81.
    Löhr M, Klöppel G. Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type 1 (insulin-dependent) diabetes mellitus and microangiopathy. Diabetologia 1987;30:757–62.PubMedGoogle Scholar
  82. 82.
    Foulis AK, Liddle CN, Farquharson MA, Richmond JA, Weir RS: The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20-years of age in the United Kingdom. Diabetologia 1986;29:267–74.PubMedGoogle Scholar
  83. 83.
    Pipeleers D, Ling Z. Pancreatic cells in insulin-dependent diabetes. Diabetes Metabolism Reviews 1992;8:209–27.PubMedGoogle Scholar
  84. 84.
    Roep BO. The role of T-cells in the pathogenesis of type 1 diabetes: from cause to cure. Diabetologia 2003;46:305–21.PubMedGoogle Scholar
  85. 85.
    Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PGF, Gamble DR. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. New Eng J Med 1985;313:353–60.PubMedGoogle Scholar
  86. 86.
    Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol 2008;155:173–81.Google Scholar
  87. 87.
    Bingley PJ, Bonifacio E, Gale EAM: Can we really predict IDDM? Diabetes 1993;42:213–20.PubMedGoogle Scholar
  88. 88.
    In t Veld P, Lievens D, De Grijse J, Ling Z, Van Der Auwera B, Pipeleers-Marichal M, Gorus F, Pipeleers D. Screening for insulitis in adult autoantibody-positive organ donors. Diabetes 2007;56:2000–4.Google Scholar
  89. 89.
    Butler AE, Galasso R, Meier JJ, Basu R, Rizza RA, Butler PC. Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of ketoacidosis. Diabetologia 2007;50:2323–31.PubMedGoogle Scholar
  90. 90.
    Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC. Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration. Diabetologia 2005;48:2221–28.PubMedGoogle Scholar
  91. 91.
    Dotta F, Censini S, van Halteren AGS, Marselli L, Masini M, Dionisi S, Mosca F, Boggi U, Muda AO, Del Prato S, Elliott JF, Covacci A, Rappuoli R, Roep BO, Marchetti P. Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent onset type 1 diabetic patients. Proc Natl Acad Sci 2007;104:5115–20.PubMedGoogle Scholar
  92. 92.
    Ahrén B, Thorsson O. Increased insulin sensitivity is associated with reduced insulin and glucagon secretion and increased insulin clearance in man. J Clin Endocrinol Metab 2003;88:1264–70.PubMedGoogle Scholar
  93. 93.
    Cerasi E, Ktorza A. Anatomical and functional plasticity of pancreatic beta-cells and type 2 diabetes. Med Sci (Paris) 2007;23:885–94.Google Scholar
  94. 94.
    Parsons JA, Brelje TC, Sorenson RL. Adaptations of islets of Langerhans to pregnancy; increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinol 1992;130:1459–66.Google Scholar
  95. 95.
    Edström K, Cerasi E, Luft R. Insulin response to glucose infusion during pregnancy. A prospective study of high and low insulin responders with normal carbohydrate tolerance. Acta Endocrinol. 1974;75:87–104.PubMedGoogle Scholar
  96. 96.
    Westermark P, Wilander E, Westermark GT, Johnson KH. Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals. Diabetologia 1987;30:887–92.PubMedGoogle Scholar
  97. 97.
    Opie E. The relation of diabetes mellitus to lesions of the pancreas. Hyaline degeneration of the islands of Langerhans. J Exp Med 1901;5:527–40.PubMedGoogle Scholar
  98. 98.
    Clark A, Saad MF, Nezzer T, Uren C, Knowler WC, Bennett PH, Turner RC. Islet amyloid polypeptide in diabetic and non-diabetic Pima Indians. Diabetologia 1990; 33:285–9.PubMedGoogle Scholar
  99. 99.
    Westermark P. Fine structure of islets of Langerhans in insular amyloidosis. Virchows Arch A Patol Anat 1973;359:1–18.Google Scholar
  100. 100.
    Butler PC, Chou J, Carter WB, Wang YN, Bu BH, Chang D, Chang JK, Rizza RA. Effects of meal ingestion on plasma amylin concentration in NIDDM and non-diabetic humans. Diabetes 1990;39:752–56.PubMedGoogle Scholar
  101. 101.
    Sanke T, Hanabusa T, Nakano Y, Oki C, Bishimura S, Kondo M, Nanjo K. Plasma islet amyloid polypeptide (Amylin) levels and their responses to oral glucose in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1991;34:129–32.PubMedGoogle Scholar
  102. 102.
    Maloy AL, Longnecker DS, Greenberg ER. The relation of islet amyloid to the clinical type of diabetes. Human Pathol 1981;12:917–22.Google Scholar
  103. 103.
    Zhao HL, Lai FM, Tong PC, Zhong DR, Yang D, Tomlinson B, Chan JC. Prevalence and clinicopathological characteristics of islet amyloid in Chinese patients with type 2 diabetes. Diabetes 2003;52:2759–66.PubMedGoogle Scholar
  104. 104.
    Clark A, Nilsson MR. Islet amyloid: a complication of islet dysfunction or an aetiological factor in type 2 diabetes. Diabetologia 2004;47:157–69.PubMedGoogle Scholar
  105. 105.
    Borromeo CM, Pottier X, In t Veld PA, Pipeleers-Marichal MA, Kaufman L, Pipeleers DG, Van Schravendijk CF. Heterogeneity in distribution of amyloid-positive islets in type-2 diabetic patients. Virchows Arch 2005;446:232–8.PubMedGoogle Scholar
  106. 106.
    Clark A, Wells CA, Buley ID, Cruickshank JK, Vanhegan RI, Matthews DR, Cooper GJ, Holman RR, Turner RC. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res 1988;9:151–9.PubMedGoogle Scholar
  107. 107.
    Sempoux C, Guiot Y, Dubois D, Moulin P, Rahier J. Human type 2 diabetes: morphological evidence for abnormal beta-cell function. Diabetes 2001;50 Suppl:S172–7.PubMedGoogle Scholar
  108. 108.
    Klöppel G, Löhr M, Habich K, Oberholzer M, Heitz PU. Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. Surv Synth Pathol Res 1985;4:110–25.PubMedGoogle Scholar
  109. 109.
    Butler AE, Janson J, Soeller WC, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52:102–10.PubMedGoogle Scholar
  110. 110.
    Haataja L, Gurlo T, Huang CJ, Butler PC. Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis. Endocr Rev 2008;29:303–16.PubMedGoogle Scholar
  111. 111.
    Janson J, Laedtke T, Parisi JE, O Brien P, Petersen RC, Butler PC. Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 2004;53:474–81.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Department of PathologyVrije Universiteit BrusselBrusselsBelgium

Personalised recommendations