Objective To explore the effects of rapamycin on blood glucose level and insulin resistance in diet-induced obese mice. MethodsHealthy 4 week-old male C57BL/6 mice were fed with high fat diet (HF,n=18)or normal chow (normal control, NC, n=18) for 8 weeks. Both control and obese mice were treated with placebo, rapamycin [2 mg/kg,intraperitonealy (ip), Qod, n=6] and 2.37% leucine-containing drinking water (n=6) for 2 weeks, respectively. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and morphological studies for pancreatic islets were performed. ResultsThe normal mice treated with rapamycin showed a significant increase of glucose level at 30 minutes after glucose challenge in comparison with the placebo- (P=0.038) and leucine-treated (P =0.035) groups. The rapamycin-treated obese mice showed a significantly elevated fasting glucose level compared with the placebo-treated obese mice (P =0.031), and a higher glucose level at 30 minutes after glucose challenge than that in the placebo-treated mice (P=0.013) and leucine-treated mice (P =0.041). The normal mice after rapamycin treatment had a decreased insulin sensitivity than those with placebo treatment (P =0.039). Rapamycin treatment significantly reduced the peritoneal white adipose mass in both normal (P<0.001) and obese mice (P =0.013)than in the placebo controls. ConclusionsRapamycin had significant effect on glucose metabolism in mice. The impairment of glucose metabolism in normal mice after rapamycin treatment is correlated with decreased glucose tolerance, while the impairment of glucose metabolism in obese mice is resulted from reduced insulin secretion and increased insulin resistance.