雷帕霉素对KKAy小鼠体重及胰岛素抵抗的影响

The effects of rapamycin on body weight and insulin resistance in KKAy mice

目的探讨雷帕霉素对KKAy小鼠体重及胰岛素抵抗(IR)的影响。方法16周KKAy小鼠34只,随机分为对照组(NC组,12只)、雷帕霉素治疗组(R组,12只)、胰岛素治疗组(Ins组,10只),6只同龄C57BL与5只KKAy小鼠作为治疗前对照。结果治疗前KKAy小鼠体重、血糖、TG明显高于C57BL小鼠(体重:36.2±1.9gvs29.3±1.0g;血糖:13.4±1.7mmol/Lvs7.8±0.5mmol/L;TG:1.59±0.16mmol/Lvs0.75±0.09mmol/L;P均<0.01)。治疗4周后:R组体重(33.7±2.3g),低于NC组(38.2±1.5g)和Ins组(37.4±1.1g),差异有统计学意义(P均<0.05);R组血糖(17.2±7.3mmol/L),低于NC组(29.1±3.2mmol/L),差异有统计学意义(P<0.05);治疗8周后:R组体重(32.2±3.1g),低于NC组(39.3±2.8g),差异有统计学意义(P<0.05);血糖(18.2±3.7mmol/L),低于NC组(24.4±5.1mmol/L),差异无统计学意义(P=0.06)。胰岛素敏感试验表明:R组在注射胰岛素60min后,血糖降幅明显大于NC组(4.88±0.73mmol/Lvs2.65±2.12mmol/L,P<0.05)。结论雷帕霉素可减轻KKAy小鼠体重、改善IR、降低血糖。

Objective To investigate the effects of rapamycin on the body weight and insulin resistance in KKAy mice,a model of type 2 diabetes. Methods Five KKAy and six C57BL mice aged 16 weeks were randomly selected as pre-treatment control Others were randomized to receive physiological saline（group C, n=12）, rapamycin（group R, n=12） and long-effective insulin（group I, n=10）. The body weight and blood glucose level were evaluated at pre-treatment,4 and 8 weeks after the initiation of treatment, The insulin sensitivity test was conducted at 5^th week in group C and group R. Results The KKAy mice manifested obesity and higher levels of glucose and triglyceride as compared with C57BL mice. After 4 weeks of treatment, group R had a significantly lower levels of body weight （33.7±2.3 g vs 37.4± 1.1 g of group C, P〈0.05 vs 38.2±1.5 g of group I, P〈0.05） and of blood glucose （ 17.2± 7.3 mmol/L vs 29. 1 ±3.2 mmol/L of group C, P 〈0.05 ; vs 26.4 ± 4.3 mmol/L of group I, P〈0.09）. At 8 week treatment, the body weight in group R was still lower than in group C（32.3±3.1 g vs 39.3±2.8 g,P〈0.05）. The glucose level of group R was lower than that of group C （18.2±3.7 mmol/L vs 24.4±5.1 retool/L） but didn＇t get statistical difference （P〈0.06） The insulin sensitivity test revealed that the level of glucose decreased rapidly and was significantly lower in group R at 60 minutes after insulin injection as compared with group C（4.88〈0.73 mmol/L vs 2.65〈2.12 mmol/L,P〈0.05）. Conclusions Rapamycin can decrease the body weight, blood glucose level, and can improve the insulin resistance in KKAy mice.