Skoglund G, Ahrén B, Lundquist I
Department of Pharmacology, University of Lund, Sweden.
Diabetes Res. 1987 Oct;6(2):81-4.
The pattern of islet lysosomal enzyme activities, islet insulin concentration and the plasma levels of insulin and glucose were studied in freely fed mice after the in vivo administration of diazoxide in doses known to induce crinophagy in islet beta-cells. After diazoxide treatment at time 0 and at 18 hr, the plasma glucose levels at 20 hr were markedly enhanced from 6.6 +/- 0.2 mmol/l (controls) to 27.2 +/- 2.7 mmol/l (diazoxide). Inhibition of insulin secretion by diazoxide was reflected in the insulinogenic index, which was reduced by approximately 40% (p less than 0.01) in the diazoxide-treated animals, who also displayed an increased concentration of islet insulin (+50%; p less than 0.01). Moreover, we found that the activities of certain lysosomal enzymes in islet tissue were markedly increased following diazoxide treatment. Thus the activities of the acid phosphatase, (+57%; p less than 0.02) the hexosaminidase N-acetyl-beta-D-glucosaminidase, (+52%; p less than 0.001), and the carboxyl proteinase cathepsin D (+41%; p less than 0.001), were all enhanced after diazoxide, whereas the activity of another lysosomal enzyme, the glycogen hydrolysing acid amyloglucosidase, was not altered by diazoxide treatment. The present data thus indicate that the morphological observation of diazoxide-induced crinophagy in pancreatic beta-cells has a biochemical correlate in enhanced levels of certain islet lysosomal enzyme activities known to participate in degradative processes. The results also suggest that islet lysosomal enzyme activities and/or lysosome populations can be modulated by a relative independence from each other.
在给自由摄食的小鼠体内注射已知能诱导胰岛β细胞发生自噬性溶酶体消化的剂量的二氮嗪后，研究了胰岛溶酶体酶活性模式、胰岛胰岛素浓度以及胰岛素和葡萄糖的血浆水平。在0小时和18小时给予二氮嗪处理后，20小时时的血浆葡萄糖水平从6.6±0.2毫摩尔/升（对照组）显著升高至27.2±2.7毫摩尔/升（二氮嗪组）。二氮嗪对胰岛素分泌的抑制作用反映在胰岛素生成指数上，在接受二氮嗪处理的动物中该指数降低了约40%（p<0.01），这些动物的胰岛胰岛素浓度也有所增加（+50%；p<0.01）。此外，我们发现二氮嗪处理后胰岛组织中某些溶酶体酶的活性显著增加。因此，酸性磷酸酶的活性（+57%；p<0.02）、己糖胺酶N-乙酰-β-D-葡糖胺酶的活性（+52%；p<0.001）以及羧基蛋白酶组织蛋白酶D的活性（+41%；p<0.001）在二氮嗪处理后均增强，而另一种溶酶体酶糖原水解酸性淀粉葡萄糖苷酶的活性未因二氮嗪处理而改变。因此，目前的数据表明，胰腺β细胞中二氮嗪诱导的自噬性溶酶体消化的形态学观察在参与降解过程的某些胰岛溶酶体酶活性水平升高方面具有生化关联。结果还表明，胰岛溶酶体酶活性和/或溶酶体群体可以相互相对独立地进行调节。
