The Effect of Infection with Venezuelan Equine Encephalomyelitis Virus, Strain TC-83, upon Insulin Secretion from Isolated Islets of Langerhans

Abstract

Viruses have been implicated in the etiology of diabetes mellitus in both man and laboratory animals. Inoculation with the attenuated vaccine strain (TC-83) of Venezuelan equine encephalomyelitis (VEE) virus was reported to cause carbohydrate intolerance and impaired immunoreactive insulin (IRI) release in golden Syrian hamsters and in rhesus monkeys. Since VEE TC-83 is used to immunize at-risk laboratory personnel working with VEE viruses, reports of a possible diabetogenic effect prompted experiments designed to determine the effects of infection with VEE TC-83 upon golden Syrian hamsters and Hartley guinea pigs. Complex interactions of physiological mechanisms influence insulin release from islets of Langerhans. Studying insulin release from isolated islets is a technique that precludes enhancement or suppression of insulin release by physiologic factors other than those introduced into the incubation media. Islets of Langerhans were isolated from golden Syrian hamsters and Hartley guinea pigs in the acute or convalescent stages of infection with VEE TC-83. These islets were incubated with a glucose challenge to determine whether infection with the TC-83 virus altered the quantity of insulin released. Insulin release from hamster islets was not impaired by TC-83 infection of the host. Neither different doses of VEE TC-83 nor different time intervals after infection affected insulin secretion. Viral growth curves performed in the isolated islets demonstrated replication of the virus does not occur. Immunofluorescent staining was performed to determine the presence of the VEE TC-83 virus in the pancreases of hamsters 48-hr after inoculation. Virus was not demonstrated by such staining techniques. Viremia studies confirmed that hamsters experimentally inoculated with VEE TC-83 were infected with the virus. Viral plaques of the TC-83 were grown from splenic preparations of VEE TC-83 inoculated hamsters. Glucose tolerance tests were performed upon the guinea pigs 30-days after inoculation with the TC-83. "Postinfected" guinea pigs showed normal carbohydrate responses to the glucose tolerance tests (GTTs) when compared with the responses of uninfected guinea pigs. IRI values are not available for the studies with guinea pigs. Since the only available first antibody is made in guinea pigs, a rabbit anti-porcine insulin antibody was produced for use in the radioimmunoassay (RIA). The rabbit anti-porcine insulin antibody has a high specificity, but unacceptably low sensitivity. These experiments suggest that infection with the VEE TC-83 virus in hamsters does not impair insulin release from isolated islets of Langerhans. TC-83 does not replicate in vitro in isolated islets nor can it be demonstrated by immunofluorescence in the islets from hamsters infected in vivo possible factor in the etiology of carbohydrate intolerance or diabetes mellitus in the hamster.