The role of viruses in type I diabetes: two distinct cellular and molecular pathogenic mechanisms of virus-induced diabetes in animals

Diabetologia
H S Jun, J W Yoon

Abstract

Type I (insulin-dependent) diabetes mellitus results from the progressive loss of pancreatic beta cells. Environmental factors are believed to play an important part in the development of Type I diabetes by influencing the penetrance of diabetes susceptibility genes. As one environmental factor, the virus has long been considered to play a part in this disease. To date 13 different viruses have been reported to be associated with the development of Type I diabetes in humans and in various animal models. The most clear and unequivocal evidence that a virus induces diabetes in animals comes from studies on the D variant of the encephalomyocarditis (EMC-D) virus in mice and the Kilham rat virus (KRV) in rats. The infection of genetically susceptible strains of mice with a high titre of EMC-D virus results in the development of diabetes within 3 days. This is largely due to the rapid destruction of beta cells by the replication of the virus within the beta cells. In contrast, the infection of mice with a low titre of EMC-D virus results in a limited replication of the virus before the induction of neutralizing anti-virus antibody and the subsequent recruitment of activated macrophages. The Src kinases, particularly hck, play an imp...Continue Reading

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