Insulin restores neuronal nitric oxide synthase expression in streptozotocin-induced diabetic rats.
Nitric oxide (NO) is known to play an important role in the pathophysiology of insulin-dependent diabetic mellitus (IDDM). In an attempt to investigate the relation between insulin and NO in IDDM, the present study employed male Wistar rats to induce IDDM by intravenous injection of streptozotocin (STZ). Four groups of rats were used; untreated normal control group, insulin treated STZ group, vehicle-treated STZ control, and one group of age-matched rats which were orally supplied with glucose to increase plasma glucose (glucose-challenged rats). Changes of the activity and gene expression of neuronal nitric oxide synthase (nNOS) were examined in cerebellum and kidney of these groups. The activity of nNOS in cerebellum, determined by conversion of [3H] L-arginine to [3H] L-citrulline, in STZ-induced diabetic rats was markedly lower than normal rats. Insulin treatment reversed the nNOS activity. Similar reversion by insulin treatment was also obtained in the gene expression of nNOS. However, the activity and gene expression of nNOS in glucose-challenged rats were not different from those in normal rats. The role of hyperglycemia can thus be ruled out. These findings indicated that an impairment of nNOS in the brain of rats with IDDM is mainly due to the absence of insulin.
Yu
W J
WJ
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, ROC.
Juang
S W
SW
Chin
W T
WT
Chi
T C
TC
Chang
C J
CJ
Cheng
J T
JT
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002956:Citrulline / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D002956:Citrulline; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat