Summary
The pancreatic islets of female non-obese diabetic (NOD) mice (a model of insulin-dependent diabetes mellitus), have been examined by both light and electron microscopy. At about the age of 2 weeks, mononuclear cells began to infiltrate in or near the islets and some of these cells were in contact with the islet cells. Following this degeneration of islet B-cells took place, the process occurring in two ways. In many cells numerous secretory granules with extremely dense cores occupied the cytoplasm. Other cells, however, were filled with low-density secretory granules and the nuclei of these cells became pycnotic. After degeneration of B-cells, the islets were effaced by numerous mononuclear cells. With the onset of the diabetic state these mononuclear cells gradually disappeared, and thereafter small islets remained.
By electron microscopy, retrovirus-like particles were observed in cisternae of the rough endoplasmic reticulum in islet B-cells at all stages. With an anti-retrovirus serum (goat anti-KiMSV-NIHxeno serum), positive immunofluorescence was observed in some pancreatic islet cells of NOD mice aged 1 day and 4, 6, 8, 9, 10 and 14 weeks. It is suggested that these virus particles may be intimately related to the inflammatory reaction occurring in the islets and to the development of diabetes mellitus.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bendayan M (1982) Double immunocytochemical labeling applying the protein A-gold technique. J Histochem Cytochem 30: 81–85
Craighead JE, McLane MF (1968) Diabetes mellitus: Induction in mice by encephalomyocarditis virus. Science 162: 913–914
Flyer DC, Burakoff SJ, Faller DV (1983) Cytotoxic T lymphocyte recognition of transfected cells expressing a cloned retroviral gene. Nature 305: 815–818
Fujita H, Fujino H, Nonaka K, Tarui S, Tochino Y (1984) Retrovirus-like particles in pancreatic B-cells of NOD (non-obese diabetic) mice. Biomed Res 5: 67–70
Fujita T, Yui R, Kusumoto Y, Serizawa Y, Makino S, Tochino Y (1982) Lymphocytic insulitis in a ‘non-obese diabetic (NOD)’ strain of mice: An immunohistochemical and electron microscope investigation. Biomed Res 3: 429–443
Hummel KP, Dickie MM, Coleman DL (1966) Diabetes, a new mutation in the mouse. Science 153: 1127–1128
Iwo K, Bellomo SC, Mukai N, Craighead JE (1983) Encephalomyocarditis virus induced diabetes mellitus in mice: Long-term changes in the structure and function of islets of Langerhans. Diabetologia 25: 39–44
Kohama M, Schichiri M, Tochino Y (1979) An ultrastructural study of pancreatic islets of spontaneous diabetic mouse with insulitis. J Clin Electron Microscopy 12: 5–6
Leiter EH, Kuff EL (1984) Intracisternal type A particles in murine pancreatic B cells. Immunocytochemical demonstration of increased antigen (p73) in genetically diabetic mice. Am J Pathol 114: 46–55
Like AA, Chick WL (1970) Studies in the diabetic mutant mouse: II. Electron microscopy of pancteatic islets. Diabetologia 6: 216–242
Like AA, Appel MC, Williams RM, Rossini AA (1978) Streptozotocin-induced pancreatic insulitis in mice. Morphologic and physiologic studies. Lab Invest 38: 470–486
Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y (1980) Breeding of a non-obese, diabetic strain of mice. Exp Anim 29: 1–13
Mayer J, Bates MW, Dickie MM (1951) Hereditary diabetes in genetically obese mice. Science 113: 746–747
McLean IW, Nakane PK (1974) Periodate-lysine-paraformaldehyde fixative: a new fixative for immunoelectron microscopy. J Histochem Cytochem 22: 1077–1083
Meier H, Yerganian GA (1959) Spontaneous hereditary diabetes mellitus in Chinese hamster (Cricetulus griseus). 1. Pathological findings. Proc Soc Exp Biol Med 100: 810–815
Mellors RC, Huang CY (1966) Immunopathology of NZB/BL mice. V. Viruslike (filtrable) agent separable from lymphoma cells and identifiable by electron microscopy. J Exp Med 124: 1031–1038
Miyazaki A, Hanafusa T, Yamada K, Miyagawa J, Fujino-Kurihara H, Nakajima H, Nonaka K, Tarui S (1985) Predominance of T lymphocytes in pancreatic islets and spleen of prediabetic non-obese diabetic (NOD) mice: A longitudinal study. Clin Exp Immunol [in press]
Nakamura M, Yamada K (1967) Studies on a diabetic (KK) strain of the mouse. Diabetologia 3: 212–221
Nakhooda AF, Like AA, Chappel CI, Murray FT, Marliss EB (1976) The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diabetes 26: 100–112
Nishimura M, Makino S (1983) Breeding of obese mice strains on NOD background. The Saishin-Igaku 38: 278–283 [in Japanese]
Onodera T, Jenson AB, Yoon JW, Notkins AL (1978) Virus-induced diabetes mellitus: Reovirus infection of pancreatic β cells in mice. Science 201: 529–531
Pictet R, Orci L, Gonet AE, Rouiller C, Renold AE (1967) Ultrastructural studies of the hyperplastic islets of Langerhans of spiny mice (Acomys Cahirinus) before and during the development of hyperglycemia. Diabetologia 3: 188–211
Rayfield EJ, Seto Y (1981) Viruses. In: Brownlee M (ed) Handbook of diabetes mellitus I. Etiology/hormone physiology. Garland STPM Press, New York London, pp 95–120
Roth J, Ravazzola M, Bendayan M, Orci L (1981) Application of the protein A-gold technique for electron microscopic demonstration of polypeptide hormones. Endocrinology 108: 247–253
Seemayer TA, Tannenbaum GS, Goldman HY, Colle E (1982) Dynamic time course studies of the spontaneously diabetic BB Wistar rat. III. Light-microscopic and ultrastructural observations of pancreatic islets of Langerhans. Am J Pathol 106: 237–249
Tochino Y (1982) NOD mouse with insulitis. Immunological Diseases 4: 33–41 [in Japanese]
Yamada K, Miyazaki A, Nakajima H, Nonaka K, Tarui S (1983) Natural history of insulitis and curability of B-cell damage. An experimental study with NOD mice. In: Sakamoto N, Alberti KGMM (eds) Current and future therapies with insulin. Excerpta Medica, Amsterdam-Oxford-Princeton, pp 322–327
Yokono K, Shii K, Hari J, Yaso S, Imamura Y, Ejiri K, Ishihara K, Fujii S, Kazumi T, Taniguchi H, Baba S (1984) Production of monoclonal antibodies to islet cell surface antigens using hybridization of spleen lymphocytes from non-obese diabetic mice. Diabetologia 26: 379–385
Yoon JW, Onodera T, Notkins AL (1978) Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with Coxsackie virus B4. J Exp Med 148: 1068–1080
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fujino-Kurihara, H., Fujita, H., Hakura, A. et al. Morphological aspects on pancreatic islets of non-obese diabetic (NOD) mice. Virchows Archiv B Cell Pathol 49, 107–120 (1985). https://doi.org/10.1007/BF02912089
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02912089