Insulin sensitivity and resistin expression in nitric oxide-deficient rats.
OBJECTIVE
The aim of this study was to investigate changes in insulin sensitivity and expression of the gene encoding resistin (Retn) in adipocytes from long-term nitric oxide (NO)-deficient rats.


METHODS
Male Sprague-Dawley rats received [Formula: see text]-nitro-L: -arginine methyl ester (L-NAME 0.5 mg/ml) in their drinking water for 4 weeks, while control rats received plain drinking water. During the experimental period, changes in plasma glucose, insulin and C-peptide levels were measured. After administration of L-NAME for 4 weeks, insulin sensitivity was evaluated in vivo and in vitro. An insulin binding assay was also performed to determine the number and binding affinity of insulin receptors in adipocytes. Adipocyte Retn mRNA levels were examined using northern blotting.


RESULTS
Successful induction of NO deficiency was demonstrated by an increase in systemic blood pressure. No difference in plasma glucose levels was found between the two groups. Compared with the control rats, plasma insulin and C-peptide levels were significantly decreased in the NO-deficient rats, and insulin sensitivity was significantly increased. Insulin-stimulated glucose uptake and insulin binding capacity, but not binding affinity, were significantly increased in adipocytes isolated from NO-deficient rats. In addition, adipocyte Retn mRNA levels, but not plasma resistin levels, were significantly decreased in NO-deficient rats, and the Retn mRNA levels were negatively correlated with insulin sensitivity.


CONCLUSIONS
Insulin sensitivity was increased in NO-deficient rats and this was associated with insulin binding capacity and downregulated Retn expression. These findings suggest that NO plays a regulatory role in metabolism. Dysregulation of NO production may result in the development of metabolic disorders.
Juan
C C
CC
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan. ccjuan@ym.edu.tw
Chang
C L
CL
Chuang
T Y
TY
Huang
S W
SW
Kwok
C F
CF
Ho
L T
LT
D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D017942:Nitric Acid / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D052243:Resistin / Q000235:genetics*
D007328:Insulin; D012333:RNA, Messenger; D052243:Resistin; D017942:Nitric Acid; D019331:NG-Nitroarginine Methyl Ester