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 type 2 diabetes and investigated the effect of insulin on EL. METHODS: 237 type 2 diabetic patients on oral anti-diabetic agents, 111 type 2 diabetic patients 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 cell medium was measured. Serum EL was also measured in 16 diabetic subjects before and after starting insulin therapy. RESULTS: Serum EL level was highest in patients on oral anti-diabetic agents whereas those on insulin had similar EL level as controls (oral: 26.7+/-16.1ng/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 significantly decreased in diabetic patients after starting insulin therapy (p<0.03). CONCLUSION: Serum EL concentration was increased in type 2 diabetic patients and was associated with the degree of subclinical inflammation and exogenous insulin therapy lowered serum EL concentration.
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 type 2 diabetes and investigated the effect of insulin on EL. METHODS: 237 type 2 diabeticpatients on oral anti-diabetic agents, 111 type 2 diabeticpatients 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 cell medium was measured. Serum EL was also measured in 16 diabetic subjects before and after starting insulin therapy. RESULTS: Serum EL level was highest in patients on oral anti-diabetic agents whereas those on insulin had similar EL level as controls (oral: 26.7+/-16.1ng/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 significantly decreased in diabeticpatients after starting insulin therapy (p<0.03). CONCLUSION: Serum EL concentration was increased in type 2 diabeticpatients and was associated with the degree of subclinical inflammation and exogenous insulin therapy lowered serum EL concentration.
Authors: Jon J Hangeland; Lynn M Abell; Leonard P Adam; Ji Jiang; Todd J Friends; Lauren E Haque; James Neels; Joelle M Onorato; Alice Ye A Chen; David S Taylor; Xiaohong Yin; Thomas W Harrity; Michael D Basso; Richard Yang; Paul G Sleph; David A Gordon; Christine S Huang; Ruth R Wexler; Heather J Finlay; R Michael Lawrence Journal: ACS Med Chem Lett Date: 2018-06-15 Impact factor: 4.345