Summary
Infection of DBA2 mice with the M strain of EMC virus was used to study the effects of virusinduced diabetes on the A and B cells of the islets of Langerhans. A transient hypoglycaemia was seen in 48% of mice 2–3 days after infection and probably resulted from increased serum insulin concentrations together with inhibition of glucagon secretion at that time. Islets from hypoglycaemic mice showed no significant alterations from control level in basal or fluoride-stimulated adenylate cyclase activity. Overall, 70% of infected mice became hyperglycaemic with a maximum incidence 6 days after infection. Hyperglycaemia was accompanied by a dramatic reduction in the total pancreatic insulin content and in insulin secretory responses to glucose and theophylline, while A-cell structure and function appeared relatively unaffected in diabetic animals. Basal adenylate cyclase activity was increased in hyperglycaemic mice at 7 days after infection, while fluoride-stimulated adenylate cyclase activity was normal throughout the course of infection. Ultrastructural alterations were observed in a small proportion of B cells from two days after infection and included abnormalities of mitochondrial structure and increased electron opacity of the cytoplasm of affected cells, which subsequently led to complete necrosis. The results suggest that EMC virus specifically affects the B cells of the islets and that disturbances of A cell function may be secondary to B cell damage.
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Burch, G. E., Harb, J. M.: Characteristic ultrastructural changes in organs of newborn mice infected with EMC virus. Proc. Soc. Exp. Biol. Med.146, 1076–1086 (1974)
Coleman, T. J., Gamble, D. R., Taylor, K. W.: Diabetes in mice after Coxsackie B4 infections. Br. Med. J.1973 III, 25–27
Craighead, J. E., McLane, M. F.: Diabetes mellitus: induction in mice by encephelomyocarditis virus. Science162, 913–914 (1968)
Craighead, J. E., Kanich, R. E., Kessler, J. B.: Lesions of the islets of Langerhans in encephalomyocarditis virus-infected mice with diabetes mellitus-like disease. Am. J. Pathol.74, 287–294 (1974)
Craighead, J. E.: The role of viruses in the pathogenesis of pancreatic disease and diabetes mellitus. Prog. Med. Virol.19, 162–214 (1975)
Craighead, J. E.: Virus induced insulitis in experimental animal models. Acta Endocrinol. [Suppl. 205] (Kbh.)83, 123–126 (1976)
Gey, G. O., Gey, M. K.: Maintenance of human normal cells and tumour cells in tissue culture. Am. J. Cancer27, 45–76 (1936)
Hales, C. N., Randle, P. J.: Immunoassay of insulin with insu-lin-antibody precipitate. Biochem. J.88, 137–146 (1963)
Henquin, J. C., Malvaux, P., Lambert, A. E.: Glucagon immunoassay using polyethylene glycol to precipitate anti-bodybound hormone. Diabetologia10, 61–68 (1974)
Howell, S. L., Taylor, K. W.: Effect of glucose concentration on incorporation of [3H]leucine into insulin in isolated rabbit islets of Langerhans. Biochim. Biophys. Acta130, 519–521 (1966)
Howell, S. L., Montague, W.: Adenylate cyclase activity in isolated rat islets of Langerhans: effects of agents which alter rates of insulin secretion. Biochim. Biophys. Acta320, 44–52 (1973)
Howell, S. L., Green, I. C., Montague, W.: A possible role of adenylate cyclase in the long-term dietary regulation of insulin secretion from rat islets of Langerhans. Biochem. J.136, 343–349 (1973)
Jansen, F. K., Müntefering, H., Schmidt, W. A. K.: Virus induced diabetes and the immune system. I. Suggestion that appearance of diabetes depends on immune reactions. Diabetologia13, 545–549 (1977)
Notkins, A. L.: Virus induced diabetes mellitus. Arch. Virol.54, 1–17 (1977)
Petersen, K. G., Heilmeyer, P., Kemp, L.: Synthesis of proinsulin and large glucagon immunoreactivity in isolated Langerhans islets from EMC-virus infected mice. Diabetologia11, 21–26 (1975)
Samols, E., Tyler, J., Miahle, P.: Suppression of pancreatic glucagon release by the hypoglycaemic sulphonylureas. Lancet1969 I, 174–176
Unger, R. H., Orci, L.: Physiology and pathophysiology of glucagon. Physiol. Rev.56, 778–826 (1976)
Wellman, K. F., Amsterdam, D., Brancato, P., Volk, B. W.: Fine structure of pancreatic islets of mice infected with the M variant of the encephalomyocarditis virus. Diabetologia8, 349–357 (1972)
Zaheer, F., Howell, S. L., Taylor, K. W., Gamble, D. R.: Pancreatic insulin and glucagon content and secretion after infection of mice with EMC virus. Biochem. Soc. Trans.5, 1058–1060 (1977)
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Zaheer, F., Howell, S.L., Taylor, K.W. et al. Biochemical and ultrastructural changes in A and B cells of the islets of Langerhans of mice infected with EMC virus. Diabetologia 17, 51–57 (1979). https://doi.org/10.1007/BF01222978
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DOI: https://doi.org/10.1007/BF01222978