Trimble E R, Rausch U, Kern H F
Institut de Biochimie Clinique, Centre Medical Universitaire, Geneva, Switzerland.
Biochem J. 1987 Dec 15;248(3):771-7. doi: 10.1042/bj2480771.
Both alterations of enzyme content and a markedly decreased secretory response to selected physiological stimuli have been demonstrated previously in the pancreas of the obese Zucker rat. The purpose of the present investigation was to determine the degree to which alterations of enzyme content could be attributed to changes in enzyme biosynthesis. Amylase content of obese rats was decreased by 50%, whereas lipase and trypsinogens were significantly increased. However, the decrease in amylase content was less than might have been predicted from the rate of amylase biosynthesis (80% decrease), and the increases in content of trypsinogen(s) and lipase were greater than would have been predicted from alterations in the absolute rates of biosynthesis. In view of the rapid turnover of pancreatic enzymes under normal conditions, it seems probable that a markedly decreased secretory response to various stimuli leads to an increased content of some enzymes in the pancreas of the obese rat. Ciglitazone treatment, which decreases insulin resistance in obese animals and leads to normalization of glucose metabolism in their pancreatic tissue, restored the enzyme-synthesis rates towards normal, showing that the abnormalities of enzyme synthesis were linked to the insulin resistance rather than to the obese genotype itself. Lipid inclusion bodies were found in acinar cells of obese rats. These bodies have previously been described in acinar cells of starved animals, which, in common with the acinar tissue of the obese Zucker rat, have decreased glucose metabolism.
先前已证实，肥胖 Zucker 大鼠的胰腺存在酶含量的改变以及对特定生理刺激的分泌反应显著降低。本研究的目的是确定酶含量的改变在多大程度上可归因于酶生物合成的变化。肥胖大鼠的淀粉酶含量降低了 50%，而脂肪酶和胰蛋白酶原显著增加。然而，淀粉酶含量的降低幅度小于根据淀粉酶生物合成速率所预测的幅度（降低 80%），并且胰蛋白酶原和脂肪酶含量的增加幅度大于根据生物合成绝对速率的改变所预测的幅度。鉴于在正常情况下胰腺酶的快速周转，肥胖大鼠胰腺中某些酶含量增加似乎很可能是由于对各种刺激的分泌反应显著降低所致。西格列他唑治疗可降低肥胖动物的胰岛素抵抗，并使其胰腺组织中的葡萄糖代谢恢复正常，该治疗使酶合成速率恢复正常，表明酶合成异常与胰岛素抵抗有关，而非与肥胖基因型本身有关。在肥胖大鼠的腺泡细胞中发现了脂质包涵体。这些包涵体先前在饥饿动物的腺泡细胞中也有描述，饥饿动物与肥胖 Zucker 大鼠的腺泡组织一样，葡萄糖代谢均降低。
