高脂饲养及罗格列酮干预对α细胞功能的影响

The effect of high fat feeding and rosiglitazone intervention on pancreatic α cell in rats

目的观察高脂饲养对SD大鼠α细胞形态和功能的影响及罗格列酮干预的作用。方法8周龄雄性SD大鼠36只随机分为3组:正常饲养组(CC,n=12)、高脂饲养组(CF,n=12)、高脂饲养+罗格列酮组(Ro,n=12,罗格列酮3mg·kg-1·d-1)。饲养28周时进行静脉糖耐量试验,于给糖后0、3、5、10min各留取动脉血待测胰岛素(Ins)及胰升糖素(Gg)水平,并同时测定即时血糖。采用组织对3H-2-脱氧葡萄糖(3H-2-DG)的吸收率评估胰岛素敏感性。免疫组织化学染色检测胰腺α细胞和β细胞的变化。结果CF组Gg在0、3、5、10min时水平[(119·3±12·4、82·3±6·4、72·2±5·8、68·2±9·1)ng/L]高于CC组[(96·8±9·1、67·6±5·9、57·9±5·3、55·3±6·9)ng/L,P<0·05];Ro组[(78·4±6·0、59·4±4·0、49·9±6·2、40·9±6·0)ng/L]显著低于CF组和CC组,P<0·01。各组Ins水平无统计学差异。α细胞积分下吸光度值,CF组及Ro组均高于CC组(1661±130及1532±132比1188±104,P<0·01及P<0·05);β细胞积分下吸光度值各组未见统计学差异。CF组的肌肉、肝脏和脂肪组织3H-2-DG吸收率明显低于CC组及Ro组(P值均<0·05)。结论高脂饲养SD大鼠引起胰岛素抵抗,同时伴有α细胞增生和Gg异常高分泌。罗格列酮可部分逆转这种变化。

Objective To observe the effect of high-fat diet and rosightazone mtervention on the function of pancreatic α cell of SD rats. Methods 36 normal male SD rats, 8-week old, were randomly divided into 3 groups i. e. , a normal chow group （CC, n=12）, an isoealorie high-fat diet group （CF, n=12） , and a rosiglitazone-treated group （Ro, n=12, rosiglitazone 3mg·kg^-1·d^-1 and isoealorie high fat diat） . Triglyceride （TG） was measured every 4 weeks after feeding for 6 weeks. After 28 weeks, the secretion of insulin and glueagon （Gg） was assessed with intravenous glucose tolerance test （IVGTT） at 0, 3, 5, and 10 minutes. ^3H-2-deoxylglueose （3H-2-DG） uptake by tissues was measured to evaluate the insulin sensitivity. Results The ratio of intra-abdominal fat mass and body weight was higher in the rats of CF and Ro group than that in the rats of CC group. At the first 10 min of IVGTT, the Gg level was higher in the CF group than that in CC group [（119.3±12.4, 82.3±6.4, 72.2±5.8, 68.2±9.1） ng/L vs （96.8±9.1, 67.6±5.9, 57.9±5.3, 55.3±6.9） ng/L, P 〈0.05] and Ro group [（78.4 ±6.0, 59.4±4. 0, 49.9±6. 2, 40. 9±6.0 ） ng/L, P〈0.01] , the level was even lower in the latter group than in CC group （ P〈0.01 ）. There was no difference of insulin level among the 3 groups. By using quantitative image analysis, the integrated A （ area × A ） of α cells was significantly higher in the CF group and Ro group as compared with that in the CC group （ 1661±130 and 1532±132 vs 1188±104, P〈0.05 ）. In contrast, there was no difference among the 3 groups in the integrated A of β cells. Conclusions High-fat feeding induces insulin resistance in rats, which is associated with pancreatic α cell proliferation and abnormal Gg secretion.