Long-term oral nicotine administration reduces insulin resistance in obese rats

This study aimed to investigate the effect of long-term oral nicotine administration on insulin resistance in an animal model of obesity. Eight-week-old male Zucker fatty rats (ZFRs) were administered nicotine tartrate dihydrate (4.6 mg/kg/day) in the drinking water. The control group was pair-fed. The body weights and food intake over 8 weeks were similar in both groups. Plasma glucose levels at 3, 6, 9, 12, and 15 min after insulin administration (0.5 U/kg) in the nicotine group were significantly lower than those in the control group. The calculated K(ITT) value for the nicotine group was significantly higher than that for the control group. Wet weight of the liver in the nicotine group was significantly lower than that in the control group. Transaminases and histological examination of the liver revealed no alteration by nicotine administration. Glycogen, glycogen synthetase activity and gluconeogenesis in the liver in the nicotine group were significantly lower than those in the control group. Phosphorylase-a activity of the liver in the nicotine group was significantly higher than that in the control group. Glycogen, glycogen synthetase, and phosphorylase-a activity of skeletal muscle were similar in both groups. These results suggest that long-term oral nicotine administration may reduce insulin resistance in obese diabetic rats through a reduced hepatic glucose release and, in part, contribute to lowering blood glucose levels.