Trimble E R, Bruzzone R, Belin D
Biochem J. 1986 Aug 1;237(3):807-12. doi: 10.1042/bj2370807.
Insulin plays a major role in the control of pancreatic amylase biosynthesis. In this study we determined glucose metabolism by pancreatic acini as well as the pancreatic content of both amylase protein and amylase mRNA during development of insulin resistance in the obese Zucker rat. At age 4 weeks there were no abnormalities detected in the above parameters, although the obese animals were already hyperinsulinaemic. At 6 weeks glucose metabolism was decreased by 50% in acini from obese rats, whereas pancreatic amylase-gene expression was only slightly impaired. At 22 weeks glucose metabolism was decreased by 50%, amylase content by 55% and amylase mRNA by 60% in acinar tissue of obese rats. As expected, hyperinsulinaemia increased markedly with age. Thus development of severe insulin resistance was associated with impairment of amylase-gene expression. To decrease insulin resistance, one group of adult obese rats was treated with Ciglitazone for 4 weeks. A lowered plasma insulin concentration without alteration of food intake was taken as evidence of decreased insulin resistance. This was associated with normalization of glucose metabolism and a marked increase of both amylase content of pancreatic tissue and amylase mRNA. In conclusion, both the increase of insulin resistance with age and its partial reversal by Ciglitazone treatment appear to modulate pancreatic amylase-gene expression in the obese Zucker rat.
胰岛素在胰腺淀粉酶生物合成的调控中起主要作用。在本研究中，我们测定了肥胖 Zucker 大鼠胰岛素抵抗发展过程中胰腺腺泡的葡萄糖代谢以及胰腺中淀粉酶蛋白和淀粉酶 mRNA 的含量。4 周龄时，上述参数未检测到异常，尽管肥胖动物已经出现高胰岛素血症。6 周龄时，肥胖大鼠腺泡中的葡萄糖代谢降低了 50%，而胰腺淀粉酶基因表达仅略有受损。22 周龄时，肥胖大鼠腺泡组织中的葡萄糖代谢降低了 50%，淀粉酶含量降低了 55%，淀粉酶 mRNA 降低了 60%。正如预期的那样，高胰岛素血症随年龄显著增加。因此，严重胰岛素抵抗的发展与淀粉酶基因表达受损有关。为了降低胰岛素抵抗，一组成年肥胖大鼠用噻唑烷二酮治疗 4 周。血浆胰岛素浓度降低而食物摄入量未改变被视为胰岛素抵抗降低的证据。这与葡萄糖代谢正常化以及胰腺组织中淀粉酶含量和淀粉酶 mRNA 显著增加有关。总之，肥胖 Zucker 大鼠中胰岛素抵抗随年龄增加及其通过噻唑烷二酮治疗的部分逆转似乎都调节胰腺淀粉酶基因表达。
