The Effect of Leptin, Tumor Necrosis Factor-α (TNF-α), and Nitric Oxide (NO) Production on Insulin Resistance in Otsuka Long-Evans Fatty Rats

Adipocytokines and nitric oxide (NO) play important roles in type 2 diabetes; however, the regulatory mechanism has not been fully clarified. To investigate the role of adipocytokines and NO production on insulin resistance in type 2 diabetes, the LETO rats and the OLETF rats were fed a control diet or a high-fat diet for 4 weeks. After 4 weeks the blood levels of leptin, tumor necrosis factor-alpha (TNF-alpha), and NO were measured. As an indicator of insulin resistance, the homeostasis model assessment for insulin resistance (HOMA-R) was applied. Food intake in high-fat diet group rats was lower than in control diet group rats. The high fat diet increased body weight (BW), but did not significantly affect the HOMA-R and blood pressure (BP). Leptin and TNF-alpha levels were significantly higher in the OLETF rats than in the LETO rats, while NO levels did not change between the two groups. The high-fat diet elevated blood leptin levels, but not TNF-alpha and NO levels. The HOMA-R in the OLETF rats was correlated with leptin, but not with BP, BW, TNF-alpha or NO. NO showed an inverse correlation with BP. In conclusion, leptin, TNF-alpha, and NO may each regulate insulin sensitivity through their own unique pathways. The elucidation of the regulatory mechanism of adipocytokines and NO may give a clue to clarify the pathophysiology of insulin resistance.