The Pattern of Neural Elements in the Islets of Normal and Diseased Pancreas and in Isolated Islets
Abstract
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.
Downloads
References
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.
Copyright (c) 2011 Parviz M Pour, Murat Saruc
This work is licensed under a Creative Commons Attribution 4.0 International License.
As a member of Publisher International Linking Association, PILA, iMedPub Group’s JOP follows the Creative Commons Attribution License and Scholars Open Access publishing policies. Journal of the Pancreas is the Council Contributor Member of Council of Science Editors (CSE) and following the CSE slogan Education, Ethics, and Evidence for Editors.