Letter | Published:

Long-term complications of virus-induced diabetes mellitus in mice

Naturevolume 296pages566568 (1982) | Download Citation



In man, the early metabolic abnormalities associated with diabetes mellitus are followed by various long-term complications1. The cause of these complications is not clear, but they may be secondary to persistent abnormalities in blood glucose levels2. In mice, several viruses can infect and destroy pancreatic β cells and produce acute-onset insulin-dependent diabetes mellitus (IDDM) characterized by hypoinsulinaemia, hypergly-caemia, glycosuria, polydypsia and polyphagia3. The virus most studied is the M variant of encephalomyocarditis (EMC) virus4,5. Long-term complications, however, have been difficult to demonstrate because in most mice, the diabetes is transient and mild. Recently, by plaque purification, we have shown that the M variant of EMC virus actually has two stable variants: one diabetogenic (designated D) and the other nondiabetogenic (designated B). Further studies revealed that the B variant reduces the severity of the diabetes produced by the D variant6. We now report that when mice are inoculated with the D variant alone, many develop severe and prolonged hyperglycaemia followed by some of the long-term complications of diabetes, including reduced lifespan, glomerulosclerosis and ocular changes.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Rep. of the National Commission on Diabetes to the Congress of the United States (U.S. Department of Health, Education and Welfare, Government Printing Office, 1976).

  2. 2

    Cahill, G. F., Etzwiler, D. D. & Freinkel, N. New Engl. J. Med. 294, 1004–1005 (1976).

  3. 3

    Notkins, A. L. Scient. Am. 241(5), 62–73 (1979).

  4. 4

    Craighead, J. E. Prog. med. Virol. 19, 161–214 (1975).

  5. 5

    Yoon, J. W. & Notkins, A. L. Postgrad. Med. (in the press).

  6. 6

    Yoon, J. W., McClintock, P. R., Onodera, T. & Notkins, A. L. J. exp. Med. 152, 878–892 (1980).

  7. 7

    Siperstein, M. Adv. intern. Med. 18, 325–344 (1972).

  8. 8

    Cogan, D. G., Toussaint, D. & Kuwabara, T. Arch. Ophthal., N.Y. 66, 366–378 (1961).

  9. 9

    Engerman, R. L. Trans. Am. Acad. Ophthal. Oto-lar. 81, 710–715 (1976).

  10. 10

    Hayashi, K., Boucher, D. W. & Notkins, A. L. Am. J. Path. 75, 91–102 (1974).

  11. 11

    Kanich, R. E., Craighead, J. E. & Kessler, J. B. Diabetologia 9, 203–209 (1973).

  12. 12

    Heptinstall, R. H. in Pathology of the Kidney 2nd edn, 929–974 (Little, Brown & Co., London, 1974).

  13. 13

    Steen-Olsen, T. Int. Rev. exp. Path. 7, 271–304 (1969).

  14. 14

    Taylor, H. R. & Kinsey, R. A. Invest. Ophthal. vis. Sci. 20, 548–553 (1981).

  15. 15

    Ashton, N. Br. J. Ophthal. 58, 344–366 (1974).

Download references

Author information


  1. Laboratory of Oral Medicine, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, 20205, USA

    • Ji-Won Yoon
    •  & Abner Louis Notkins
  2. Clinical Branch, National Institutes of Health, Bethesda, Maryland, 20205, USA

    • Merlyn M. Rodrigues
    •  & Carol Currier


  1. Search for Ji-Won Yoon in:

  2. Search for Merlyn M. Rodrigues in:

  3. Search for Carol Currier in:

  4. Search for Abner Louis Notkins in:

About this article

Publication history



Issue Date



Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.