Behr S R, Kraemer F B
Division of Endocrinology and Metabolism, Stanford University School of Medicine, California 94305-5103.
Diabetes. 1988 Aug;37(8):1076-81. doi: 10.2337/diab.37.8.1076.
We investigated the effects of insulin deficiency and insulin treatment on the secretion of lipoprotein lipase (LPL) by murine macrophages. Streptozocin-induced insulin deficiency caused hyperglycemia and hypertriglyceridemia in mice. Peritoneal macrophages isolated from insulin-deficient mice secreted 70% less LPL activity than control mice. A 65% decrease in LPL activity in epididymal adipose tissue, without any changes in heart LPL activity, was also seen with insulin deficiency. One week of insulin treatment lowered plasma glucose and triglyceride levels in insulin-deficient mice. Additionally, 1 wk of insulin treatment increased LPL secretion by macrophages, but to only one-half of control, while normalizing adipose tissue LPL activity. One injection of insulin also increased LPL secretion by macrophages to one-half of control and normalized adipose tissue LPL activity, even though plasma glucose and triglyceride levels were not affected. In vitro insulin treatment of macrophages isolated from control or insulin-deficient mice had no effect on LPL secretion. The results suggest that insulin does not exert a direct effect on the LPL secretion by macrophages but that deficiency of insulin indirectly causes a profound decrease in macrophage LPL secretion. These changes in macrophage LPL secretion may contribute to the atherosclerotic process in diabetes mellitus.
我们研究了胰岛素缺乏和胰岛素治疗对小鼠巨噬细胞脂蛋白脂肪酶(LPL)分泌的影响。链脲佐菌素诱导的胰岛素缺乏导致小鼠出现高血糖和高甘油三酯血症。从胰岛素缺乏小鼠分离的腹腔巨噬细胞分泌的LPL活性比对照小鼠低70%。胰岛素缺乏时,附睾脂肪组织中的LPL活性降低了65%,而心脏LPL活性没有任何变化。胰岛素治疗1周可降低胰岛素缺乏小鼠的血糖和甘油三酯水平。此外,胰岛素治疗1周可增加巨噬细胞的LPL分泌,但仅为对照的一半,同时使脂肪组织LPL活性恢复正常。单次注射胰岛素也可使巨噬细胞的LPL分泌增加至对照的一半,并使脂肪组织LPL活性恢复正常,尽管血浆葡萄糖和甘油三酯水平未受影响。体外胰岛素处理从对照或胰岛素缺乏小鼠分离的巨噬细胞对LPL分泌没有影响。结果表明,胰岛素对巨噬细胞的LPL分泌没有直接作用,但胰岛素缺乏间接导致巨噬细胞LPL分泌显著减少。巨噬细胞LPL分泌的这些变化可能有助于糖尿病的动脉粥样硬化进程。