Angiotensin type 1 receptor blockers telmisartan and irbesartan activate PPARα / 中华内分泌代谢杂志

Objective To investigate the effect of telmisartan and irbesartan on PPARα transcriptional activity, and to clarify their molecular mechanisms in improving glucose and lipid metabolism. Methods The structural expression vectors, including pCMV-PPARα, pGL3-PPRE and the internal control vector pRL-TK, were transiently eo-transfected into COS-7 cells using SuperFect, the cells were eontinously cultured with various concentrations of telmisartan and irbesartan, and then the PPRE controlled luciferase activity was determined by using a dual-luciferase reporter gene assay system. PPARα mRNA and protein expression levels were detected by RT-PCR and Western blot after 3T3-L1 adipoeytes were treated with various concentrations of telmisartan or irbesartan. Results (1) Both telmisartan and irbesartan stimulated PPARα transcriptional activity in concentration-and time-dependent manners in cultured COS-7 cells with the maximal effect at 60 h, with the results increased by 3.8 and 2.6 folds respectively at the concentration of 100 μmol/L compared with control group (both P<0.01). (2) The PPARγ antagonist GW9662 did not inhibit fenofibrate, telmisartan and irbesartan-stimulated PPARα transcriptional activities. (3) Both telmisartan and irbesartan increased PPARα mRNA and protein expression levels in a dose-dependent manner in 3T3-L1 adipocytes. Conclusion Angiotensin type 1 receptor blockers, telmisartan and irbesartan, can both increase PPARα transcriptional activity, which may contribute to their metabolic effects.

Angiotensin Ⅱ receptor blocker induces the activation of peroxisome proliferator-activated receptor gamma / 中国糖尿病杂志

Objective To observe the effect of angiotensin Ⅱ receptor blockers(ARBs)on peroxisome proliferator-activated receptor gamma(PPAR-γ)and to explore its mechanism for improving glucose and lipids metabolism.Methods Dual-luciferase gene reporting system was used to reflect PPAR-γ promoter activation by irbesartan and telmisartan.RT-PCR was used to reflect PPAR-γ mRNA by activation of irbesartan and telmisartan.Results Irbesartan and telmisartan may increase COS-7 cells PPAR-γ promoter expression and increase 3T3-L1 cells PPAR-γ mRNA expression in dose and time-dependent manners.Conclusions ARB may activate PPARs system to play a role in improving the glucose and lipids metabolism

Screening of angiotensin type 1 receptor blockers with the function to activate peroxisome proliferator-activated receptor ? and ? / 解放军医学杂志

Objective To explorer the effect of angiotensin type 1 receptor blockers (ARB) on activating peroxisome proliferator-activated receptor (PPAR) ? and ?.MethodsLuciferase gene reporters of PPAR? and PPAR? were constructed in COS-7 cells.The cells were then cultured with various concentrations (0,0.01,0.1,1,10 and 100 ?mol/L) of valsartan,losartan,irbesartan or telmisartan for 12,24,36,48 and 60 hours;or co-cultured with PPAR? antagonist GW9662 (10,30?mol/L) for 1 hour,and then cultured with various concentrations (0,1 and 10?mol/L) of irbesartan or telmisartan for 12,24,36,48 and 60 hours.The peroxisome proliferator-response element (PPRE) luciferase activity was determined by Dual-Luciferase Reporter Gene Assay system.3T3-L1 cells were induced to differentiate into adipocytes,and then co-cultured with 10?mol/L of valsartan,losartan,irbesartan or telmisartan for 24 hours,and the expressions of PPAR? and PPAR? mRNA and protein were detected by RT-PCR and Western blotting respectively.ResultsStimulation of valsartan and losartan didn't increase the transcriptional activities of PPAR? and PPAR? in COS-7 cells,while of irbesartan and telmisartan significantly increased the transcriptional activity of PPAR? and PPAR? in COS-7 cells.After co-cultured with 100 ?mol/L of irbesartan or telmisartan for 48 hours,the PPAR? transcriptional activities reached their peak values (43.3?13.0 and 47.8?11.8 respectively),and were significantly higher than that of control group (4.3?0.5,P

Effects of two regimes of intensive insulin therapy for type 2 diabetes on improvement of the function of islet b cell / 解放军医学杂志

Objective To investigate the effect of continuous subcutaneous insulin injection(CSII)and multiple subcutaneous insulin injection(MSII)on islet b cell function at the onset of type 2 diabetes.Method 64 patients were randomly divided into CSII(f/m=18/20)and MSII groups(f/m=14/12).There was no significant difference in age,fasting C peptide level,fasting blood glucose level,BMI and HbA1c.The patients of both groups were given intensive insulin therapy.Once the total dosage of daily insulin was kept less than 30U and the fast blood glucose was 3.6-6.0 mmol/L,intensive insulin therapy was changed to oral administration of hypoglycin A(OHA),otherwise the intensive insulin therapy was continued.The number of patients who were switched over to oral drug was compared after one month after the intensive therapy.Result 31 patients in CSII group and 8 patients in MSII group were changed to OHA one month after intensive therapy.A significant difference existed between the two groups(?2=3.37,P