Effect of insulin on endothelial lipase in type 2 diabetes

Abstract

Objective: Endothelial lipase (EL), a new member of the triacylglycerol lipase family, modulates the metabolism of high-density lipoproteins and is upregulated by inflammatory cytokines. Since Type 2 diabetes is associated with chronic subclinical inflammation, we have determined whether serum EL concentration is increased in patients with Type 2 diabetes and investigated the effect of insulin on EL. Methods: A total of 237 patients with Type 2 diabetes on oral anti-diabetic agents, 111 patients with Type 2 diabetes on insulin therapy and 226 non-diabetic controls were recruited. Serum EL was measured by ELISA. To investigate the effect of insulin on EL production by endothelial cells, human aortic endothelial cells were incubated with insulin and EL mRNA and protein in the cell medium was measured. Serum EL was also measured in 16 diabetic subjects before and after starting insulin therapy. Results: Serum EL levels were highest in patients on oral antidiabetic agents, whereas those on insulin had similar EL levels as controls (oral: 26.7 ± 16.1 ng/ml; insulin: 23.3 ± 11.6, controls: 23.9 ± 12.0; ANOVA p=0.04). In both controls and patients on oral anti-diabetic agents, EL correlated with log(CRP) (r=0.20, p=0.003; r=0.23, p<0.001 respectively), but no correlation was seen in patients on insulin. In vitro experiments showed that insulin significantly reduced EL mRNA and protein in human aortic endothelial cells in a dose-dependent manner. Serum EL concentration also decreased significantly in diabetic patients after starting insulin therapy (p<0.03). Conclusion: Serum EL concentration was increased in patients with Type 2 diabetes and was associated with the degree of subclinical inflammation. Exogenous insulin therapy lowered serum EL concentration.