The Effects Of Intermittent High Glucose And Pioglitazone On The Adiponectin Receptors Expression Of HUVECs

Objectives: (1) To compare the effects of intermittent and constant high glucose media on the mRNA expression of adiponectin receptors(AdipoR1 and AdipoR2) in cultured human umbilical endothelial cells (HUVECs) in vitro.(2) To investigate the effect of pioglitazone on the AdipoR1 and AdipoR2 expression of HUVECs induced by intermittent high glucose.Methods: (1)HUVECs were exposed to 5.5mmol/L glucose (normal), 20mmol/L glucose (constant high glucose), and 5.5mmol/L alternating with 20mmol/L glucose per 8h (intermittent high glucose) respectively for 1d,3d, 5d. The AdipoR1 and AdipoR2 mRNA expression level in HUVECs were measured by real-time PCR. (2) After exposed to intermittent high glucose for 5d, HUVECs were incubated with pioglitazone(10-5,10-6 or 10-7mol/L) for 24 hours separately, the AdipoR1 and AdipoR2 mRNA expression level in HUVECs were also determined by real-time PCR.Results: (1) Treated with high glucose or intermittent high glucose for 1d, both adiponectin receptors of HUVECs did not change. Compared with the controls in which glucose concentration was 5.5mmol/L, the AdipoR1 expression was suppressed when HUVECs were exposed to high glucose for 3 days, which even more in intermittent high glucose than in constant high glucose(both P<0.05). The expression of AdipoR1 mRNA was downregulated significantly with exposure time increasing. But the treatment of glucose on HUVECs may not affect the expression of AdipoR2 mRNA .(2)After exposed to intermittent high glucose for 5 days, HUVECs were treated with pioglitazone(10-5,10-6 or 10-7mol/L) for 24h. 10-5, 10-6 mol/L of pioglitazone treatment enhanced AdipoR1 mRNA level (both P < 0.05) , which induced in a dose-dependent manner. But there is no effect on the level of AdipoR2.Conclusions: (1) High glucose and intermittent high glucose may both due to the downregulation of the expression of AdipoR1 in HUVECs, but the latter downregulated at a high level. (2) Pioglitazone can inhibit significantly the downregulation of AdipoR1 in HUVECs induced by intermittent high glucose in a dose-dependent manner. The AdipoR1 may play an important role in adiponectin sensitivity amelioration of endothelial cells.