In an attempt to know the role of nitric oxide in the disease of insulin-de
pendent diabetic mellitus (IDDM), the present study examined the change of
nitric oxide synthase (NOS) both the activity and gene expression in cerebr
ocortex of streptozotocin-induced diabetic rats (STZ-diabetic rats). The ac
tivity of NOS determined by conversion of [H-3] L-arginine to [H-3] L-citru
lline was markedly decreased in STZ-diabetic rats. Northern blot showed tha
t STZ-diabetic rats expressed a lower mRNA level of neuronal NOS (nNOS). We
stern blot showed a similar decrease of nNOS in STZ-diabetic rats. However,
the NOS activity was increased in rats receiving repeated supply of glucos
e named glucose-challenged rats. Although the mRNA level of nNOS was not ch
anged in the glucose-challenged rats, the immunoblot of nNOS was also decre
ased in glucose-challenged rats. These findings suggested that NOS was lowe
red in the brain of STZ-diabetic rats in a way unrelated to the increase of
glucose. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.