ATTEMPTS TO PHARMACOLOGICALLY MODULATE PROLACTIN LEVELS AND TYPE-1 AUTOIMMUNE DIABETES IN THE NONOBESE DIABETIC (NOD) MOUSE

Prolactin (PRC) is well known for its stimulatory effects on various c omponents of the immune response. Experimentally induced high levels o f FRL have been shown to correlate with the worsening of several autoi mmune diseases. In contrast, lowering PRL levels may protect from the autoimmune process. We investigated in both sexes of NOD mice a sponta neous model of autoimmune type 1 diabetes, the effects of two drugs, a dopaminergic agonist, bromocriptine (BRC, 10 mg/kg), which is assumed to inhibit PRL secretion, and a dopaminergic antagonist, metocloprami de (MCP, 5 mg/kg), which in contrast stimulates PRL secretion, on the incidence of diabetes, the severity of insulitis, and PRC and glucose levels. Chronic treatment of NOD mice with MCP slightly aggravated dev elopment of diabetes. The dopamine antagonist tended to accelerate the onset of diabetes in females and significantly increased the number o f islets with peri-insulitis in both sexes. The weak deleterious effec ts exerted by MCF in NOD mice may be related to its stimulatory action on PRL release. Contrary to the expected results, the dopamine agonis t BRC did not protect from autoimmune diabetes. In contrast, the drug appeared to accelerate diabetes onset in males and significantly incre ased the number of islets showing insulitis in both sexes. This study underlines the complexity of the action of BRC which in NOD mice only transiently inhibits the release of PRL. Moreover, the aggravating act ions of BRC may be related to the marked hyperglycemic effect of the d rug observed in male and female NOD mice. (C) 1995 Academic Press Limi ted