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

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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