Effect of insulin on pancreatic regeneration and gene expression after major pancreatectomy

为探讨胰岛素促进胰腺再生的分子机制，本研究旨在探讨胰岛素促进胰腺再生的分子机制，包括胰腺腺泡细胞c-fos、c-myc基因表达、鸟氨酸脱羧酶(ODC)活性、DNA合成和锌摄取。所有的狗在手术后立即发生糖尿病。将动物分为胰岛素治疗组和非胰岛素治疗组。对照组12只狗接受了简单的剖腹手术。残余胰腺中c-fos和c-myc基因的表达在胰腺切除后早期即可诱导表达，1d后达高峰。观察两组在胰岛素治疗前后原癌基因mRNA表达的变化。此后，升高的信使核糖核酸水平在7天内降至对照水平。残余胰腺的ODC活性和DNA合成也显著增加，分别在术后第3天和第5天达到最高水平。在胰岛素治疗组中，这两个水平都显著高于对照组。ODC活性和DNA合成的增强在14d内降至对照水平。在无胰岛素处理的情况下，残余胰腺中的锌浓度逐渐下降，而在胰岛素处理的动物中，从第5天开始显著升高。ODC和DNA合成活性的增强与组织锌浓度显著相关。这些结果表明，残余胰腺中的oDC活性和dna合成不仅受到胰岛素的刺激，也受到锌的刺激，而原癌基因的表达不是由胰岛素诱导的，而是由胰腺切除后早期释放的未知因子(S)诱导的。

The effect of insulin on pancreatic regeneration after approximately 95% distal pancreatectomy was investigated in dogs To elucidate the molecular mechanism of the insulin action in promoting pancreatic regeneration, the present studu was focused on the gene expressions of c-fos and c-myc, elevation of ornithine decarboxylase (ODC) activity as well as DNA synthesis, and zinc uptake in pancreatic acinar cells. All the dogs developed diabetes mellitus immediately after surgery. The animals were divided tinto two groups : the insulin treated group and non-insulin treated group. A control group of twelve dogs received simple laparotomies. Expressions of c-fos and c-myc mRNAs in the remnant pancreas were induced at the early phase afer pancreatectomy reaching their maximal levels in one day. Inductions of mRNA expression of the proto-oncogenes were obseved in both groups with and without insulin treatment. Elevated mRNA levels thereafter decreased to the control levels within 7 days. Activities of ODC and DNA synthesis in the remnant pancreas also increased remarkably and reached their maximal levels at 3 and 5 days after pancreatectomy, respectively. both levels were significantly higher in the insulin treated group. the enhanced activities of ODC and DNA synthesis decreased to the control levels within 14 days. Concentration of zinc in the remnant pancreas gradually decrease in the absence of insulen treatment, wheresd it increased significantly in the insulin treated animals from 5 days. The enhanced activites of ODC and DNA synthesis correlated significantly with the tissue zinc concentration. These results suggest that ODC activity and DNA synthesis are stimulated not only by insulin but also bu zinc in the remnant pancreas, while the expressions of proto-oncogenes are not induced by insulin but rather by unknown factor (s) released in the early phase after pancreatectomy