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目的研究9,10-二羟基硬脂酸(DHSA)对KKAy糖尿病小鼠糖耐量、胰岛素敏感性的影响。方法将48只雄性KKAy小鼠随机分为4组,每组12只,分别给予含4%DHSA高脂饲料、2%DHSA高脂饲料、4%橄榄油高脂饲料和4%玉米油高脂饲料。饲养5周时进行糖耐量实验、第6周进行胰岛素敏感性实验。体外检测DHSA对CV-1的PPAR-α和PPAR-γ的激活作用。结果在葡萄糖耐量试验中,4%DHSA组KKAy小鼠葡萄糖负荷后0.5h、1h血糖及血糖曲线下面积明显低于其它各组;4%DHSA组在注射胰岛素0.5h、1h后的血糖较低,反映对胰岛素的敏感性高于其它各组(P<0.05);4%DHSA组体重明显低于4%玉米油高脂饲料组(P<0.05)。DHSA在低浓度(5～20μmol/L)时没有激活CV-1细胞PPAR-γ的作用,而在50～100μmol/L浓度时具有激活PPAR-γ活性的作用,且具有一定的剂量-效应关系,但其活性远低于罗格列酮(ROSI)。DHSA没有激活CV-1细胞PPAR-α的作用。结论 DHSA改善KKAy糖尿病小鼠糖耐量和增加胰岛素敏感性,可能与提高PPAR-γ活性有关。
Objective To investigate the effect of 9,10-dihydroxystearic acid (DHSA) on glucose tolerance and insulin sensitivity in KKAy diabetic mice. Methods Forty eight male KKAy mice were randomly divided into 4 groups with 12 rats in each group, which were given 4% DHSA high fat diet, 2% DHSA high fat diet, 4% olive oil high fat diet and 4% corn oil high fat feed. Glucose tolerance test was conducted 5 weeks after feeding, and insulin sensitivity test was performed 6 weeks later. In vitro activation of PPAR-α and PPAR-γ by DHSA on CV-1 was examined. Results In the glucose tolerance test, the area under the curve of blood glucose and blood glucose of KKAy mice in 4% DHSA group at 0.5h and 1h after glucose load was significantly lower than that in other groups. The blood glucose of 4% DHSA group after 0.5h injection of insulin for 1h was lower (P <0.05). The body weight of 4% DHSA group was significantly lower than that of 4% corn oil high fat diet group (P <0.05). DHSA did not activate PPAR-γ in CV-1 cells at low concentration (5-20 μmol / L), and PPAR-γ activity at 50-100 μmol / L with a dose-response relationship , But its activity is much lower than rosiglitazone (ROSI). DHSA did not activate PPAR-α in CV-1 cells. Conclusion DHSA improves glucose tolerance and insulin sensitivity in KKAy diabetic mice, which may be related to the increase of PPAR-γ activity.