Enhanced serum glucocorticoid levels mediate the reduction of serosal mast cell numbers in diabetic rats.
Rats turned diabetic by treatment with alloxan exhibit a significant reduction in serosal mast cell numbersin parallel with decreased insulin levels in the plasma. Our aim was to investigate the putative involvement of endogenous glucocorticoid hormone in this phenomenon. The findings indicated that rats treated with alloxan responded with an increase in levels of serum corticosterone concomitantly with decreased mast cell numbers in the pleural space. We found that either surgical bilateral adrenalectomy or pretreatment with the steroid antagonist RU 486 (20 mg/kg, i.p.) impaired the drop in pleural mast cell counts in alloxinated rats. Administration of insulin (15 U/kg) prevented the increase in corticosterone levels and restored pleural mast cell levels in diabetic animals. In addition, treatment of naive rats with corticosterone (0.5 mg/kg, s.c.) or dexamethasone (0.1 mg/kg, s.c.), for 3 consecutive days, led to a reduction in the number of mast cells recovered from the pleural cavity as noted in diabetic animals. In contrast, insulin reduced serum corticosterone levels and induced a significant elevation in pleural mast cell numbers in naive rats. We conclude that there is a causative relationship between increased levels of glucocorticoids and down-regulation of mast cell numbers associated with the diabetic state, both phenomena clearly sensitive to insulin.
Diaz
B
B
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Barreto
E
E
Cordeiro
R
R
Perretti
M
M
Martins
M
M
Silva
P
P
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D005938:Glucocorticoids / Q000097:blood*; D006943:Hyperglycemia / Q000097:blood; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology*; D015735:Mifepristone / Q000494:pharmacology*; D010994:Pleura / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D015735:Mifepristone; D003345:Corticosterone