Effect of gliotoxin on development of diabetes mellitus in diabetes-prone BB/Wor rats

The object of this investigation was to determine if gliotoxin, an immunomodulating fungal secondary metabolite, is capable of preventing the development of autoimmune diabetes mellitus in diabetes-prone BB/Wor rats. Chronic treatment, consisting of 1 microg gliotoxin/g of body wt administered three times weekly from the age of 30 days through 120 days, reduced the incidence of diabetes from 90% diabetic by 120 days among vehicle-treated animals to 56% diabetic among gliotoxin-treated animals. This result was significant by life table analysis. Animals treated with gliotoxin maintained lower serum glucose levels even in the pre-diabetic state than control (vehicle-treated) rats. Gliotoxin at levels used in this study showed no appreciable effect on the viability of rat insulinoma (RIN 38) cells in culture and only slightly decreased their insulin secretion. Animals chronically treated with gliotoxin showed weight gains comparable to those seen in controls, and the effect of gliotoxin on peripheral blood leukocyte counts was not significant. The possibility that gliotoxin exerted its effect through immunomodulating effects was implied by the loss of white pulp in splenic follicles of gliotoxin-treated animals.