Human insulin B chain but not A chain decreases the rate of diabetes in BBrats

The autoimmune response seen in insulin-dependent diabetes mellitus (IDDM) includes a humoral immune response against human insulin. Early insulin tre atment has been used to prevent IDDM in the rodent models of IDDM, and a pr evention trial is underway in humans. The metabolic effects of insulin may not be involved in this prevention since, in NOD mice, the use of metabolic ally inert human insulin B chain was effective. We wished to ascertain whet her immunization of diabetes-prone BB/W rats with insulin B chain, A chain, or both could alter the incidence of diabetes. Immunizations began by 30 d ays of age and the rats were followed until 120 days of age. Only immunizat ion with insulin B chain plus adjuvant was effective in reducing the rate o f diabetes. All immunization frequencies were effective, but a significantl y lower rate of diabetes was achieved with injections every week. All of th e doses tested resulted in significantly lower rates of diabetes. These dat a confirm in the BE rat model that immunization with insulin B chain in the presence of adjuvant can reduce diabetes incidence. The absence of any met abolic effect of B chain and the requirement for adjuvant suggest that this effect is mediated via modulation of the autoimmune response. (C) 1999 Els evier Science Ireland Ltd. All rights reserved.