Abstract:

Objective To investigate the main mechanism of losartan in treatment of insulin resistance in 3T3-L1 adipocytes. Methods The model of insulin resistance in 3T3-L1 adipocytes was induced by dexamethasone. Model control group (without treatment with any drug), losartan group (treatment with 1 μmol/L, 10 μmol/L and 100 μmol/L losartan for 48 h respectively) and wortmannin+losartan group were divided. Adipocytes in wortmannin+losartan group were pretreated with 100 nmol/L wortmannin, phosphatidylinositol 3-kinase (PI3K) inhibitor for 20 min, and were treated with 100 μmol/L losartan for 48 h. The size of adipocytes was observed, glucose oxidase method was employed to measure the glucose concentration in supernatant of culture fluid, and Western blotting was adopted to detect the expression of PI3K and insulin receptor substrate 1 (IRS-1) and level of IRS-1 serine phosphorylation in adipocytes. Results Compared with model control group, the size of adipocytes significantly reduced (P<0.01), the glucose concentration in supernatant of culture fluid significantly decreased (P<0.01), the expression of PI3K and IRS-1 significantly increased (P<0.01). The level of IRS-1 serine phosphorylation significantly decreased compared with model control group (P<0.01), but the effect could be blocked by wortmannin. Conclusion Losartan could significantly decrease the cell size and increase the consumption of glucose in 3T3-L1 adipocytes with insulin resistance, and the mechanism might be associated with PI3K pathway.

Key words: losartan, adipocyte, insulin resistance