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.

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