棕榈酸对胰岛的脂毒性及非诺贝特的保护作用

Lipotoxicity of palmitic acid on islets and protecting effect of fenofibrate

目的 探讨棕榈酸对胰岛功能的影响和非诺贝特对棕榈酸所致胰岛脂毒性的保护作用及机制。方法 分离大鼠胰岛,分6组:对照组、棕榈酸0. 2mmol/L组(PA0. 2)和0. 4mmol/L(PA0. 4)组,非诺贝特组(FF, 5×10-6 mol/L)及PA0. 2+FF组、PA0. 4+FF组。培养24h分别测定基础胰岛素(BIS)和葡萄糖刺激的胰岛素分泌(GSIS);RT PCR或实时PCR测定胰岛素(INS)、胰腺十二指肠同源异型盒因子1 (PDX 1)、葡萄糖转运蛋白2(GLUT2)和PPARαmRNA表达。结果 (1)与对照组比较PA0. 2组和PA0. 4组BIS增加,GSIS升高倍数减少,且PA0. 4组变化幅度更明显;FF组BIS、GSIS与对照组比较差异无统计学意义;PA0. 2+FF组比PA0. 2组BIS减少31%,GSIS增加29%;PA0. 4+FF组比PA0. 4组BIS减少56%,GSIS增加121%;PA0. 2+FF组与PA0. 4+FF组GSIS增加幅度低于对照组(均P<0. 05 )。( 2 )与对照组比较,PA0. 2组和PA0. 4组PDX 1、INS和GLUT2的表达降低(P<0. 05),但PPARα表达不受影响。(3)与PA0. 2组和PA0. 4组比较,PA0. 2+FF组、PA0. 4 +FF组的INS、GLUT2、PDX 1、PPARαmRNA表达增加(P<0. 05 )。结论 棕榈酸抑制胰岛GLUT2、INS、PDX 1mRNA表达,抑制胰岛素转录合成。非诺贝特增加PPARαmRNA表达,与棕榈酸共存时增强GLUT2、INS、PDX 1mRNA表达。

Objective To observe the effects of palmitic acid (PA) and fenofibrate (FF) on rat islets. Methods Rat islets were isolated with collagenase digestion and divided into 6 groups: control group, PA0.2 group (with 0.2 mmol/L PA), PA0.4 group(with0.4mmol/LPA),FF group (with 5×10 -6 mol/L fenofibrate), PA0.2+FF group and PA0.4 +FF group. After being cultured 24 hours with PA in the presence or absence FF, baseline insulin secretion (BIS) and glucose stimulated insulin secretion (GSIS) were examined. The mRNA levels of insulin(INS), pancreas-duodenum homeobox-1 (PDX-1), glucose transport protein 2 (GLUT-2) and PPARα were determined by RT-PCR or real-time PCR. Results (1)In both PA0.2 and PA0.4 groups, BIS was increased and GSIS increase was impaired as compared with control group (P<0.01); GSIS was increased by 29% and BIS reduced by 31% in PA0.2 +FF group as compared with those in PA0.2 group; GSIS increased by 121% and BIS reducedby56%inPA0.4+FFgroup as compared with PA0.4 group (P<0.05). GSIS of PA0.2 +FF or PA0.4 +FF group were lower than those in control or FFgroup,andtheywerehigher than those in PA0.2 or PA0.4 group respectively. (2)In both PA0.2 and PA0.4 groups, INS, PDX-1 and GLUT2 mRNA expressions (P<0.05) were suppressed as compared with control group, and no effects were found on PPARα(P>0.05). Expressions of INS, PDX-1 ,GLUT2 and PPARα mRNA were enhanced in PA0.2 +FF group and PA0.4 +FF group as compared with the two groups without FF respectively (all P<0.05). Conclusion PA inhibits INS,PDX-1 and GLUT2 mRNA expressions in islets of normal rat, while fenofibrate improves their expression, suggesting that fenofibrate ameliorates lipotoxicity induced by PA in islets of normal rats.