Skip to main content
SpringerLink
Log in

Alteration of the langerhans islets in pancreatic cancer patients

  • Published:
International Journal of Pancreatology Aims and scope Submit manuscript

Summary

An abnormal glucose metabolism occurs in up to 80% of pancreatic cancer patients shortly or a few months before the first clinical admission. Reasons for this abnormality are obscure. We investigated immunohistochemically the pattern of islets in 14 pancreatic cancer specimens and used 14 chronic pancreatitis samples and 10 normal pancreata as controls. To study the topographical relationship of these islets to the cancer, islets in four different arbitrary zones within and around the cancer were evaluated. Ten out of 14 cancer specimens showed a significant loss of β cells (p<0.005) and eight of them also showed a significant increase of α cells (p<0.005), all of them from hyperglycemic patients. Most affected islets were found within zone 1 (intratumoral) and zone 2 (peritumoral), to a lesser extent in zone 3 (acini close to tumor) and none in zone 4 (acini remote from tumor). No comparable changes were found in chronic pancreatitis patients. The incidence of 72% with alteration of islets in our material correlates with the frequency of abnormal glucose levels in human pancreatic cancer patients. Our findings support the notion that islet cell abnormalities is likely caused by substances released from cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zimmermann B: Diabetes and gross lesions of the pancreas. J Clin Endocrinol Metab 1954; 14: 481.

    Article  Google Scholar 

  2. Kessler II. Cancer and diabetes mellitus. A review of the literature. J Chronic Dis 1971; 23: 579–600.

    Article  PubMed  CAS  Google Scholar 

  3. Cuzick J, Babiker AG. Pancreatic cancer, alcohol, diabetes mellitus and gallbladder disease. Int J Cancer 1989; 43: 415–421.

    Article  PubMed  CAS  Google Scholar 

  4. Permert J, Ihse I, Jorfeldt L, von Schenck H, Arnquist HJ, Larsson J. Improved glucose metabolism after subtotal pancreatectomy for pancreatic cancer. Br J Surg 1993; 80: 1047–1050.

    Article  PubMed  CAS  Google Scholar 

  5. Gullo L. Diabetes and the risk of pancreatic cancer. Ann Oncol 1999; 10: 79–81.

    Article  PubMed  Google Scholar 

  6. Ching C, Rhodes J. Diabetes mellitus and pancreatic disease. IN Textbook of diabetes. Pickup J, Williams G, eds. Oxford, UK, Blackwell Scientific Publications, 1986; 256–262.

    Google Scholar 

  7. Ihse I, Isaksson G. Pancreatic carcinoma: diagnosis and treatment. Clin Gastroenterol 1984; 13: 961–984.

    PubMed  CAS  Google Scholar 

  8. Kaji H, Inoue K, Miyashita T, Uchida K, Takahashi K, Tobe T. Relationship between glucose tolerance and quantitative changes of islet cells in chronic obstructive pancreatitis due to pancreatoduodenal cancer. Am J Gastroenterol 1991; 86: 1020–1026.

    PubMed  CAS  Google Scholar 

  9. Klüppel G, Bommer G, Commandeur G, Heitz P. The endocrine pancreas in chronic pancreatitis. Immunocytochemical and ultrastructural studies. Virchows Arch A Pathol Pathol Anat 1978; 377: 157–174.

    Article  Google Scholar 

  10. Murphy R, Smith F. Abnormal carbohydrate metabolism in pancreatic carcinoma. Med Clin North Am 1963; 47: 397–405.

    PubMed  CAS  Google Scholar 

  11. Cersosimo E, Pisters PW, Pesola G, McDermott K, Bajorunas D, Brennan MF. Insulin secretion and action in patients with pancreatic cancer. Cancer 1991; 67: 486–493.

    Article  PubMed  CAS  Google Scholar 

  12. Ishikawa O, Ohhigashi H, Wada A, et al. Morphologic characteristics of pancreatic carcinoma with diabetes mellitus. Cancer 1989; 64: 1107–1112.

    Article  PubMed  CAS  Google Scholar 

  13. Ariyama J, Suyama M, Ogawa K, et al. The detection and prognosis of small pancreatic carcinoma. Int J Pancreatol 1990; 7: 37–47.

    PubMed  CAS  Google Scholar 

  14. Basso D, Brigato L, Veronesi A, Panozzo MP, Amadori A, Plebani M. The pancreatic cancer cell line MIA PaCa2 produces one or more factors able to induce hyperglycemia in SCID mice. Anticancer Res 1995; 15: 2585–2588.

    PubMed  CAS  Google Scholar 

  15. Hayashida CY, Suzuki K, Fujiya H, Koizumi M, Toyota T, Goto Y. Morphometrical quantitation of pancreatic endocrine cells in patients with carcinoma of the pancreas. Tohoku J Exp Med 1983; 141: 311–322.

    Article  PubMed  CAS  Google Scholar 

  16. Berkowitz D, Greenberg L, Glassmann S. The intravenous tolbutamide test as a diagnostic aid in carcinoma of the pancreas. Am J Med Sci 1963; 243: 150–154.

    Article  Google Scholar 

  17. Linde J, Nilsson LH, Barany FR. Diabetes and hypoglycemia in chronic pancreatitis. Scand J Gastroenterol 1977; 12: 369–373.

    Article  PubMed  CAS  Google Scholar 

  18. Lankisch PG, Otto J, Erkelenz I, Lembcke B. Pancreatic calcifications: no indicator of severe exocrine pancreatic insufficiency. Gastroenterology 1986; 90: 617–621.

    PubMed  CAS  Google Scholar 

  19. Committee WHO: Diabetes Mellitus. Technical report series, Geneva, ed., WHO, 1985.

  20. Pour PM, Kazakoff K, Dulany K. A new technique for simultaneous demonstration of 4 tumor-associated antigens in pancreatic cancer cells. Zentralbl Pathol 1994; 140: 397–401.

    PubMed  CAS  Google Scholar 

  21. Chari ST, Singer MV. The problem of classification and staging of chronic pancreatitis. Proposals based on current knowledge of its natural history [see comments]. Scand J Gastroenterol 1994; 29: 949–960.

    Article  PubMed  CAS  Google Scholar 

  22. Sarles H, Adler G, Dani R, et al. The pancreatitis classification of Marseilles-Rome 1988. Scand J Gastroenterol 1989; 24: 641–642.

    Article  PubMed  CAS  Google Scholar 

  23. Gullo L, Perzilli R, Morselli-Labate AM. Diabetes and the risk of pancreatic cancer. Italian Pancreatic Cancer Study Group [see comments]. N Engl J Med 1994; 331: 81–84.

    Article  PubMed  CAS  Google Scholar 

  24. Permert J, Ihse I, Jorfeldt L, von Schenck H, Arnqvist HJ, Larsson J. Pancreatic cancer is associated with impaired glucose metabolism. Eur J Surg 1993; 159: 101–107.

    PubMed  CAS  Google Scholar 

  25. Friedman GD, van den Eeden SK. Risk factors for pancreatic cancer: an exploratory study. Int J Epidemiol 1993; 22: 30–37.

    Article  PubMed  CAS  Google Scholar 

  26. Larsen S. Diabetes mellitus secondary to chronic pancreatitis. Dan Med Bull 1993; 40: 153–162.

    PubMed  CAS  Google Scholar 

  27. Fogar P, Basso D, Panozzo MP, et al. C-peptide pattern in patients with pancreatic cancer. Anticancer Res 1993; 13: 2577–2580.

    PubMed  CAS  Google Scholar 

  28. Permert J, Larsson J, Fruin AB, et al. Islet hormone secretion in pancreatic cancer patients with diabetes. Pancreas 1997; 15: 60–68.

    Article  PubMed  CAS  Google Scholar 

  29. Basso D, Plebani M, Fogar P, et al. Beta-cell function in pancreatic adenocarcinoma. Pancreas 1994; 9: 332–335.

    Article  PubMed  CAS  Google Scholar 

  30. Basso D, Valerio A, Brigato L, Panozzo MP, Miola M, Lucca T, Ujka F, Zaninotto M, Avogaro A, Plebani M. An unidentified pancreatic cancer cell product alters some intracellular pathways of glucose metabolism in isolated rat hepatocytes. Pancreas 1997; 15: 132–138.

    Article  PubMed  CAS  Google Scholar 

  31. Permert J, Adrian TE, Jacobsson P, Jorfelt L, Fruin AB, Larsson J. Is profound peripheral insulin resistance in patients with pancreatic cancer caused by a tumor-associated factor? Am J Surg 1993; 165: 61–66; Discussion 66–67.

    Article  PubMed  CAS  Google Scholar 

  32. Schwartz SS, Zeidler A, Moossa AR, Kuku SF, Rubenstein AH. A prospective study of glucose tolerance, insulin, C-peptide, and glucagon responses in patients with pancreatic carcinoma. Am J Dig Dis 1978; 23: 1107–1114

    Article  CAS  Google Scholar 

  33. Soler NG, Exon PD, Paton A. Carbohydrate tolerance and insulin responses in obstructive jaundice. Br Med J 1974; 4: 447–449.

    PubMed  CAS  Google Scholar 

  34. Kalser MH, Barkin J, MacIntyre JM. Pancreatic cancer. Assessment of prognosis by clinical presentation. Cancer 1985; 56: 397–402.

    Article  PubMed  CAS  Google Scholar 

  35. Ingelfinger F. The diagnosis of cancer of the pancreas. New Eng J Med 1946; 235: 653–661.

    Article  CAS  Google Scholar 

  36. Glicksman A, Rawson R. Diabetes and altered carbohydrate metabolism in patients with cancer. Cancer 1956; 9: 1127–1134.

    Article  PubMed  CAS  Google Scholar 

  37. Permert J, Larsson J, Westermark GT, et al. Islet amyloid polypeptide in patients with pancreatic cancer and diabetes. N Engl J Med 1994; 330: 313–318.

    Article  PubMed  CAS  Google Scholar 

  38. Unger RH, Orci L. Glucagon and the A cell: physiology and pathophysiology (first two parts). N Engl J Med 1981; 304: 1518–1524.

    Article  PubMed  CAS  Google Scholar 

  39. Unger RH, Orci L. Glucagon and the A cell: Physiology and pathophysiology (second of two parts). N Engl J Med 1981; 304: 1575–1580.

    Article  PubMed  CAS  Google Scholar 

  40. Li J, Ding X, Adrian T. A factor from pancreatic cancer cells stimulates glucagon secretion from INR1G9 cells. Pancreas 1997; 15: 443.

    Google Scholar 

  41. Aguilar-Parada E, Eisentraut AM, Unger RH. Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci 1969; 257: 415–419.

    Article  PubMed  CAS  Google Scholar 

  42. Mallinson CN, Bloom SR, Warin AP, Salmon PR, Cox B. A glucagonoma syndrome. Lancet 1974; 2: 1–5.

    Article  PubMed  CAS  Google Scholar 

  43. Barnes AJ, Bloom SR. Pancreatectomised man: a model for diabetes without glucagon. Lancet 1976; 1: 219–221.

    Article  PubMed  CAS  Google Scholar 

  44. Ammann RW. Clinical aspects and differential diagnosis of chronic pancreatitis. Emphasis on the long term course in 258 patients. Schweiz Med Wochenschr 1980; 110: 1322–1327.

    PubMed  CAS  Google Scholar 

  45. Petrin P, Chiappetta A, Del Favero G, Farini R, Pedrazzoli S. Chronic pancreatitis and diabetes. Minerva Med 1983; 74: 31–38.

    PubMed  CAS  Google Scholar 

  46. James O, Agnew JE, Bouchier IA. Chronic pancreatitis in England: a changing picture? Br Med J 1974; 2: 34–38.

    PubMed  CAS  Google Scholar 

  47. Kloeppel G. Islet histopathology in diabetes mellitus. Pancreatic Pathology. Kloeppel G, Heitz P, eds. New York, Churchill Livingstone, 1984, pp. 154–193.

    Google Scholar 

  48. Bank S, Marks IN, Vinik AI. Clinical and hormonal aspects of pancreatic diabetes. Am J Gastroenterol 1975; 64: 13–22.

    PubMed  CAS  Google Scholar 

  49. Wang F, Larsson J, Abdiu A, et al. Dissociated secretion of islet amyloid polypeptide and insulin in serum- free culture media conditioned by human pancreatic adenocarcinoma cell lines. Int J Pancreatol 1997; 21: 157–164.

    PubMed  CAS  Google Scholar 

  50. Ding X, Flatt PR, Permert J, Adrian TE. Pancreatic cancer cells selectively stimulate islet beta cells to secrete amylin. Gastroenterology 1998; 114: 130–138.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE

    Bruno M. Schmied, Alexis B. Ulrich, Hosei Matsuzaki, Chunhui Li & Parviz M. Pour

  2. Department of Visceral and Transplantation Surgery, Insel Hospital, Bern, Switzerland

    Bruno M. Schmied, Helmut Friess & Markus W. Böchler

  3. Department of Surgery, Rheinische Friedrich-Wilhelms-University, Bonn, Germany

    Alexis B. Ulrich

  4. Department of Surgery II, Kumamoto University, Kumamoto, Japan

    Hosei Matsuzaki

  5. Department of Surgery, Bergen University, Bergen, Norway

    Åke Andrøn-Sandberg

  6. Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE

    Thomas E. Adrian

  7. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE

    Parviz M. Pour

Authors
  1. Bruno M. Schmied
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexis B. Ulrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hosei Matsuzaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chunhui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helmut Friess
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Markus W. Böchler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Åke Andrøn-Sandberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thomas E. Adrian
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Parviz M. Pour
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Parviz M. Pour.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmied, B.M., Ulrich, A.B., Matsuzaki, H. et al. Alteration of the langerhans islets in pancreatic cancer patients. International Journal of Pancreatology 28, 187–197 (2000). https://doi.org/10.1385/IJGC:28:3:187

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/IJGC:28:3:187

Keywords

Search

Navigation