11 胰升血糖素样肽-1对肝切除后肝细胞胞浆游离钙影响的实验研究

目的:探讨胰升血糖素样肽-1（GLP-1）对肝切除后肝细胞胞浆游离钙的影响。方法:将大鼠随机分2组，A组不切肝,B组切肝65%。于术后第1，3，5天收集血标本5mL测定血糖、GLP-1、胰岛素(In)和胰升血糖素(G1)。同时用酶法分离制备肝细胞悬液。以Fura-2/AM荧光指示剂，用荧光分光光度仪检测肝切除后肝细胞的荧光强度及GLP-1对荧光强度的影响。结果:B组肝切除术后血糖明显增高（P<0.05），血浆GLP-1也明显高于A组（P<0.001），尤以术后第1天更显著; In则明显下降（P<0.001）,而G1手术后升高，但差异无显著性（P>0.05），术后In/GL值明显下降（P<0.05）。所测正常肝细胞［Ca2+］i为（707.46±122.59）nmol/L，肝切除术后第1，3，5天肝细胞［Ca2+］i较正常肝细胞略降低（P>0.05）;加入GLP-1后肝细胞［Ca2+］i略有升高（P>0.05）。结论:大鼠肝切除术后存在明显胰岛素抵抗，主要系因胰岛素水平明显下降，致In/G1值也明显降低的结果;GLP-1的拟胰岛素作用并非通过增加肝细胞［Ca2+］in而实现的。

The influence of glucagon-like peptide-1 on cytosolic free calcium ion concentration in isolated rat hepatocytes after hepatectomy

Objective To investigate the effect of glucagon-like peptide-1(GLP-1) on cytosolic free calcium ion concentration( [ca2 ]i) in isolated rat hepatocytes after hepatectomy.Methods The rats were allocated randomly to two groups: The rats of group one did not undergo hepatectomy.The rats of group two had 65 % liver resection.The blood specimen taken from vena cava was mensurated for glucose,insulin,glucagon,and glucagon-like peptide-1(GLP-1) on the first,third and fifth day after hepatectomy.The [ca2 ]i in isolated rat hepatocytes was investigated by using fura-2 fluoresence,and then,in vitro,the effect of GLP-1 on the [ca2 ]i in hepatocytes was investigated in 2 groups.Results The blood glucose value in group two was significantly higher than that in group one after operation(P<0.05),especially on the first day.The plasma GLP-1 value was also significantly higher than that of group one(P<0.001).The level of serum insulin was decreased obviously(P<0.001),while the value of glucagon was increased,but not significantly,which led to reduction of the ratio of insulin to glucagon.The [ca2 ]i in hepatocytes on the first,third and fifth day after hepatectomy was decreased slightly(P>0.05) compared with that of group one.In vitro,GLP-1 produced a slightly increase in the [ca2 ]i in hepatocytes(P>0.05).Conclusions After hepatectomy,in rats is associated with an obvious insulin resistance,mainly due to the level of serum insulin was obviously decreased(P<0.001),and the value of glucagon was increased,which led to reduced ratio of insulin to glucagon.GLP-1 is insulinomimetic upon glucose metabolism in hepatic tissue,which acting through specific receptors is not associated to [ca2 ]i increase.