Tavangar K, Murata Y, Pedersen M E, Goers J F, Hoffman A R, Kraemer F B
Department of Medicine, Stanford University School of Medicine, California 94305.
J Clin Invest. 1992 Nov;90(5):1672-8. doi: 10.1172/JCI116039.
Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity and development of hypertriglyceridemia. In the current experiments the mechanisms involved in the regulation of LPL have been examined in control rats, streptozocin-induced diabetic rats, and diabetic rats treated chronically or with a single injection of insulin. Diabetes decreased adipose tissue LPL activity partially by decreasing immunoreactive LPL protein and the steady-state levels of LPL mRNA, but primarily by reducing the catalytic activity of LPL. Both chronic and acute insulin increased adipose tissue LPL activity by correcting the defect in the catalytic activity of LPL and increasing immunoreactive LPL protein; however, only chronic insulin restored LPL mRNA levels to normal. In the heart, LPL activity tended to be elevated with diabetes in parallel to an increase in immunoreactive LPL protein even though levels of LPL mRNA declined. Both chronic and acute insulin normalized LPL activity and immunoreactive LPL protein, while only chronic insulin corrected the levels of LPL mRNA. No changes in the catalytic activity of LPL in heart were detected among the groups. Thus, diabetes and insulin treatment regulate LPL expression pretranslationally, translationally, and post-translationally, with tissue-specific differences apparent in the mechanisms involved.
糖尿病与脂蛋白脂肪酶（LPL）活性降低及高甘油三酯血症的发生有关。在当前实验中，已在对照大鼠、链脲佐菌素诱导的糖尿病大鼠以及长期或单次注射胰岛素治疗的糖尿病大鼠中研究了LPL调节的相关机制。糖尿病通过降低免疫反应性LPL蛋白和LPL mRNA的稳态水平，部分降低了脂肪组织LPL活性，但主要是通过降低LPL的催化活性。慢性和急性胰岛素均通过纠正LPL催化活性缺陷并增加免疫反应性LPL蛋白，从而增加了脂肪组织LPL活性；然而，只有慢性胰岛素将LPL mRNA水平恢复至正常。在心脏中，尽管LPL mRNA水平下降，但糖尿病时LPL活性倾向于升高，同时免疫反应性LPL蛋白增加。慢性和急性胰岛素均使LPL活性和免疫反应性LPL蛋白恢复正常，而只有慢性胰岛素纠正了LPL mRNA水平。各组间未检测到心脏中LPL催化活性的变化。因此，糖尿病和胰岛素治疗在翻译前、翻译中和翻译后调节LPL表达，且所涉及的机制存在明显的组织特异性差异。
