The Pattern of Neural Elements in the Islets of Normal and Diseased Pancreas and in Isolated Islets

  • Parviz M Pour UNMC Eppley Cancer Center and Department of Pathology and Microbiology, University of Nebraska Medical Center. Omaha, NE, USA
  • Murat Saruc Acibadem Hospital. Istanbul, Turkey
Keywords: beta III-tubulin protein, human, Insulin-Secreting Cells, Islets of Langerhans, Pancreatic Neoplasms, Pancreatitis, Chronic, Tissue Donors


Context The association between islet cells and neural elements, the so-called “neuro-insular complex”, has been known for centuries. Objective We examined the expression of beta-III tubulin, in normal pancreases from organ donors, surgical specimens of chronic pancreatitis, surgical specimens of ductal type carcinoma, isolated and purified islets of a 57-year-old male and the pancreases of adult Syrian golden hamsters by immunohistochemistry using a monoclonal antibody to beta-tubulin. Results In the normal pancreas of humans and hamsters, beta-III tubulin was expressed in alpha- and beta-cells, but not in PP cells, neural fibers and gangliae. Occasionally, intra-and peri-insular neural elements were also found. In chronic pancreatitis and pancreatic cancer samples, the number of beta-cells and the immunoreactivity of the beta-III tubulin antibody in islet cells were decreased in most cases. In cultured human islets, devoid of neural elements, no correlation was found between the expression of beta-III tubulin and islet cell hormones. Conclusion Beta-III tubulin is only expressed in the islets derived from the dorsal pancreas and in neural elements. In chronic pancreatitis and pancreatic cancer swelling of intra- and peri-insular nerves occurs, possibly in response to the loss of beta-cells. The secretion of insulin and the expression of beta-tubulin seem to be regulated by nerves.

Image: Multi-labeling of normal pancreatic islets.


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Tezel E, Nagasaka T, Nomoto S, Sugimoto H, Nakao A. Neuroendocrine-like differentiation in patients with pancreatic carcinoma. Cancer 2000; 89:2230-6.

Schneider MB, Standop J, Ulrich A, Wittel U, Friess H, Andren-Sandberg A, Pour PM. Expression of nerve growth factors in pancreatic neural tissue and pancreatic cancer. J Histochem Cytochem 2001; 49:1205-10.

Koizumi H, Morita M, Mikami S, Shibayama E, Uchikoshi T. Immunohistochemical analysis of trka neurotrophin receptor expression in human non-neuronal carcinomas. Pathol Int 1998; 48:93-101.

Shibayama E, Koizumi H. Cellular localization of the trk neurotrophin receptor family in human non-neuronal tissues. Am J Pathol 1996; 148:1807-18.

Dustin P. Microtubules. Sci Am 1980; 243:66-76.

Standop J, Itami I, Saruc M, Yalniz M, Pour PM. 6th Conference of European Hepato-Pancreati-Biliary Association. Heidelberg, Germany, 2005.

Schmied BM, Ulrich A, Matsuzaki H, Ding X, Ricordi C, Moyer MP, et al. Maintenance of human islets in long-term culture. Differentiation 2000; 66:173-80.

Schmied BM, Ulrich A, Matsuzaki H, Ding X, Ricordi C, Weide L, et al. Transdifferentiation of human islet cells in a long-term culture. Pancreas 2001; 23:157-71.

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.

Schmied BM, Ulrich AB, Matsuzaki H, Li C, Friess H, Bochler MW, et al. Alteration of the langerhans islets in pancreatic cancer patients. Int J Pancreatol 2000; 28:187-97.

Pour PM, Schmied BM, Ulrich AB, Friess H, Andren-Sandberg A, Buchler MW. Abnormal differentiation of islet cells in pancreatic cancer. Pancreatology 2001; 1:110-6.

Schmied BM, Ulrich AB, Friess H, Buchler MW, Pour PM. The patterns of extrainsular endocrine cells in pancreatic cancer. Teratog Carcinog Mutagen 2001; 21:69-81.

Ushiki T, Watanabe S. Distribution and ultrastructure of the autonomic nerves in the mouse pancreas. Microsc Res Tech 1997; 37:399-406.

Watari N. Fine structure of nervous elements in the pancreas of some vertebrates. Z Zellforsch Mikrosk Anat 1968; 85:291-314.

Sternini C, Brecha N. Immunocytochemical identification of islet cells and nerve fibers containing calcitonin gene-related peptide-like immunoreactivity in the rat pancreas. Gastroenterology 1986; 90:1155-63.

Oomori Y, Iuchi H, Ishikawa K, Satoh Y, Ono K. Immunocytochemical study of tyrosine hydroxylase and dopamine beta-hydroxylase immunoreactivities in the rat pancreas. Histochemistry 1994; 101:313-23.

Luiten PG, ter Horst GJ, Koopmans SJ, Rietberg M, Steffens AB. Preganglionic innervation of the pancreas islet cells in the rat. J Auton Nerv Syst 1984; 10:27-42.

Honjin R. The innervation of the pancreas of the mouse, with special reference to the structure of the peripheral extension of the vegetative nervous system. J Comp Neurol 1956; 104:331-71.

Esterhuizen AC, Spriggs TL, Lever JD. Nature of islet-cell innervation in the cat pancreas. Diabetes 1968; 17:33-6.

Persson-Sjogren S, Forsgren S, Kjorell U, Taljedal IB. Intrinsic and extrinsic npy nerves in transplanted neuroinsular complexes. Peptides 1998; 19:1233-40.

Ulrich AB, Standop J, Schmied BM, Schneider MB, Lawson TA, Pour PM. Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of bop. Pancreatology 2002; 2:519-27.

Ulrich AB, Schmied BM, Standop J, Schneider MB, Lawson TA, Friess H, et al. Differences in the expression of glutathione s-transferases in normal pancreas, chronic pancreatitis, secondary chronic pancreatitis, and pancreatic cancer. Pancreas 2002; 24:291-7.

Edwards RH, Rutter WJ, Hanahan D. Directed expression of ngf to pancreatic beta cells in transgenic mice leads to selective hyperinnervation of the islets. Cell 1989; 58:161-70.

Shorr SS, Bloom FE. Fine structure of islet-cell innervation in the pancreas of normal and alloxan-treated rats. Z Zellforsch Mikrosk Anat 1970; 103:12-25.

Bishop APJ. The anatomy, organization and ultrastructure of the islets of Langerhans. Oxford, UK: Blackwell Science. pp. 6.1, 1997.

Permert J, Larsson J, Westermark GT, Herrington MK, Christmanson L, Pour PM, et al. Islet amyloid polypeptide in patients with pancreatic cancer and diabetes. N Engl J Med 1994; 330:313-8.

Saruc M, Pour PM. Diabetes and its relationship to pancreatic carcinoma. Pancreas 2003; 26:381-7.

Multi-labeling of normal pancreatic islets
How to Cite
PourP., & SarucM. (2011). The Pattern of Neural Elements in the Islets of Normal and Diseased Pancreas and in Isolated Islets. JOP. Journal of the Pancreas, 12(4), 395-403.