Possible mechanisms in the pathogenesis of virus-induced diabetes mellitus.
Insulin-dependent diabetes mellitus results from destruction of pancreatic beta cells. Viruses and autoimmunity have been implicated as possible causes of beta cell destruction in genetically predisposed individuals. The evidence for viruses comes largely from experiments in animals, but several studies in humans point to viruses as triggers in the pathogenesis of diabetes in some cases. In animal models, at least 4 different possible mechanisms for virus-induced diabetes have been proposed. The first mechanism is direct cytolytic infection of pancreatic beta cells. One group of viruses, including encephalomyocarditis virus, Mengovirus 2T, and Coxsackie B viruses, can directly infect and destroy pancreatic beta cells independent of autoimmune processes. The second mechanism is triggering of autoimmune responses. In contrast to the encephalomyocarditis virus-induced diabetes, reovirus type 1 and rubella virus seem to be somehow associated with autoimmunity in the genesis of a diabetes-like syndrome in a certain strain of suckling mice and hamsters, respectively. The third mechanism is cumulative environmental insults. The cumulative environmental insults with viruses and beta cell toxic chemicals can result in diabetes in genetically predisposed non-human primates and certain inbred strains of mice. The fourth mechanism is persistent infection. A certain virus, such as lymphocytic choriomeningitis virus, persistently infects murine pancreatic beta cells and produces hyperglycemia. The evidence that viruses cause diabetes in humans is more circumstantial.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoon
J W
JW
Department of Microbiology and Infectious Diseases, Julia McFarlane Diabetes Research Unit, University of Calgary, Alberta, Canada.
Eun
H M
HM
Essani
K
K
Roncari
D A
DA
Bryan
L E
LE
D000818:Animals; D003384:Coxsackievirus Infections / Q000150:complications; D003921:Diabetes Mellitus, Experimental / Q000209:etiology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D004686:Encephalomyocarditis virus; D029822:Enterovirus B, Human; D004769:Enterovirus Infections / Q000150:complications*; D004781:Environmental Exposure; D006801:Humans; D008574:Mengovirus; D014777:Virus Diseases / Q000150:complications* / Q000276:immunology