Attempts to pharmacologically modulate prolactin levels and type 1 autoimmune diabetes in the non-obese diabetic (NOD) mouse.
Prolactin (PRL) is well known for its stimulatory effects on various components of the immune response. Experimentally induced high levels of PRL have been shown to correlate with the worsening of several autoimmune diseases. In contrast, lowering PRL levels may protect from the autoimmune process. We investigated in both sexes of NOD mice a spontaneous 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, metoclopramide (MCP, 5 mg/kg), which in contrast stimulates PRL secretion, on the incidence of diabetes, the severity of insulitis, and PRL and glucose levels. Chronic treatment of NOD mice with MCP slightly aggravated development of diabetes. The dopamine antagonist tended to accelerate the onset of diabetes in females and significantly increased the number of islets with peri-insulitis in both sexes. The weak deleterious effects exerted by MCP in NOD mice may be related to its stimulatory action on PRL release. Contrary to the expected results, the dopamine agonist BRC did not protect from autoimmune diabetes. In contrast, the drug appeared to accelerate diabetes onset in males and significantly increased 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 actions of BRC may be related to the marked hyperglycemic effect of the drug observed in male and female NOD mice.
Durant
S
S
CNRS URA 1461--Université René Descartes, Paris, France.
Alves
V
V
Coulaud
J
J
El Hasnaoui
A
A
Dardenne
M
M
Homo-Delarche
F
F
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001971:Bromocriptine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000473:pathology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005260:Female; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D011388:Prolactin / Q000097:blood / Q000187:drug effects*; D016896:Treatment Outcome
D001786:Blood Glucose; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D001971:Bromocriptine; D011388:Prolactin; D008787:Metoclopramide