糖复康宁提取物对SGLT2的抑制作用及降糖作用研究
|
摘要
目的研究糖复康宁提取物对钠离子-葡萄糖协同转运体2(SGLT2)的抑制作用及对二型糖尿病大鼠的降糖作用。方法通过由转染试剂Lipo 3 000介导的转基因方法构建SGLT2过表达的HEK293细胞株,考察0.01、0.03、0.1、0.3、1.0、3.0 mg/m L糖复康宁提取物对SGLT2介导的α-甲基吡喃葡萄糖苷(14C-AMG)摄入的抑制作用;应用高糖高脂饲料和链脲佐菌素制备二型糖尿病动物模型,ig低、高剂量(162、324 mg/kg)糖复康宁提取物,每天给药1次,连续给药5周,每周测定空腹血糖值,给药结束后测定糖耐量。结果与对照组比较,0.1、0.3、1.0、3.0 mg/m L的糖复康宁提取物对SGLT2介导的14C-AMG摄入均有显著抑制作用(P<0.05),IC50为0.119 mg/m L;与模型组比较,ig 162、324 mg/kg糖复康宁提取物35 d后,二型糖尿病大鼠的空腹血糖显著降低(P<0.05、0.01),糖耐量也明显改善(P<0.05)。结论糖复康宁提取物对二型糖尿病大鼠发挥显著降糖作用,其机制可能与抑制SGLT2对葡萄糖的重吸收相关。
Objective To research the inhibition of Tangfu Kangning extracts to SGLT2 and the antidiabetic effects to mice with type II diabetic. Method The SGLT2 overexpressed cell line(HEK293-SGLT2) was transfected through Lipo3000. The inhibitory effects of 0.01, 0.03, 0.1, 0.3, 1, and 3 mg/m L of Tangfu Kangning extracts on SGLT2 mediated 14 C-AMG intake were investigated. The animal model of type two diabetes was prepared with high glucose and high fat diet and streptozotocin, ig low and high dose(162, 324 mg/kg) Tangfu Kangning extract to mice, once daily, continuous for five weeks, the fasting blood glucose was measured weekly, and the glucose tolerance was measured after the end of the administration. Result Compared with control group, the Tang Fu Kang Ning extract of 0.1, 0.3, 1.0, and 3.0 mg/m L had significant inhibitory effects on SGLT2 mediated 14 C-AMG intake(P < 0.05) and IC50 was 0.119 mg/m L. The fasting blood glucose(FBG) of type II diabetes mice treated with the two dosages(162 and 324 mg/kg)of Tangfu Kangning extracts for 35 d were significantly lower than model group(P < 0.05 and 0.01). The glucose tolerances of mice treated with Tangfu Kangning extract were also improved(P < 0.05). Conclusion Tangfu Kangning extracts have significant hypoglycemic effect on type two diabetes rats, and its mechanism may be related to inhibiting the reabsorption of glucose by SGLT2.
Objective To research the inhibition of Tangfu Kangning extracts to SGLT2 and the antidiabetic effects to mice with type II diabetic. Method The SGLT2 overexpressed cell line(HEK293-SGLT2) was transfected through Lipo3000. The inhibitory effects of 0.01, 0.03, 0.1, 0.3, 1, and 3 mg/m L of Tangfu Kangning extracts on SGLT2 mediated 14 C-AMG intake were investigated. The animal model of type two diabetes was prepared with high glucose and high fat diet and streptozotocin, ig low and high dose(162, 324 mg/kg) Tangfu Kangning extract to mice, once daily, continuous for five weeks, the fasting blood glucose was measured weekly, and the glucose tolerance was measured after the end of the administration. Result Compared with control group, the Tang Fu Kang Ning extract of 0.1, 0.3, 1.0, and 3.0 mg/m L had significant inhibitory effects on SGLT2 mediated 14 C-AMG intake(P < 0.05) and IC50 was 0.119 mg/m L. The fasting blood glucose(FBG) of type II diabetes mice treated with the two dosages(162 and 324 mg/kg)of Tangfu Kangning extracts for 35 d were significantly lower than model group(P < 0.05 and 0.01). The glucose tolerances of mice treated with Tangfu Kangning extract were also improved(P < 0.05). Conclusion Tangfu Kangning extracts have significant hypoglycemic effect on type two diabetes rats, and its mechanism may be related to inhibiting the reabsorption of glucose by SGLT2.
引文
[1]Han S,Hagan D L,Taylor J R,et al.Dapagliflozin,a selective SGLT2 inhibitor,improves glucose homeostasis in normal and diabetic rats[J].Diabetes,2008,57(6):1723-1729.
[2]Gallo L A,Wright E M,Vallon V.Probing SGLT2 as a therapeutic target for diabetes:Basic physiology and consequences[J].Diab Vasc Dis Res,2015,12(2):78-89.
[3]Chao E C,Henry R R.SGLT2 inhibition--a novel strategy for diabetes treatment[J].Nat Rev Drug Discov,2010,9(7):551-559.
[4]Wu W,Dong Y,Gao J,et al.Aspartate-modified doxorubicin on its N-terminal increases drug accumulation in LAT1-overexpressing tumors[J].Can Sci,2015,106(6):747-756.
[5]Cai W,Jiang L,Xie Y,et al.Design of SGLT2 Inhibitors for the treatment of type 2 diabetes:A history driven by biology to chemistry[J].Med Chem,2015,11(4):317-328.
[6]Kanai Y,Lee W S,You G,et al.The human kidney low affinity Na+/glucose cotransporter SGLT2.Delineation of the major renal reabsorptive mechanism for D-glucose[J].J Clin Invest,1994,93(1):397-404.
[7]孙桂菊,王少康,张小强,等.Ⅱ型糖尿病大鼠模型的建立及糖尿病并发症相关指标测定[J].实验动物与比较医学,2003.23(2):79-82.
[8]熊昕,隆敏,蔡雷琴,等.一种新型的降糖药物——SGLT2抑制剂研究进展[J].重庆医科大学学报,2016(11):1172-1176.
[2]Gallo L A,Wright E M,Vallon V.Probing SGLT2 as a therapeutic target for diabetes:Basic physiology and consequences[J].Diab Vasc Dis Res,2015,12(2):78-89.
[3]Chao E C,Henry R R.SGLT2 inhibition--a novel strategy for diabetes treatment[J].Nat Rev Drug Discov,2010,9(7):551-559.
[4]Wu W,Dong Y,Gao J,et al.Aspartate-modified doxorubicin on its N-terminal increases drug accumulation in LAT1-overexpressing tumors[J].Can Sci,2015,106(6):747-756.
[5]Cai W,Jiang L,Xie Y,et al.Design of SGLT2 Inhibitors for the treatment of type 2 diabetes:A history driven by biology to chemistry[J].Med Chem,2015,11(4):317-328.
[6]Kanai Y,Lee W S,You G,et al.The human kidney low affinity Na+/glucose cotransporter SGLT2.Delineation of the major renal reabsorptive mechanism for D-glucose[J].J Clin Invest,1994,93(1):397-404.
[7]孙桂菊,王少康,张小强,等.Ⅱ型糖尿病大鼠模型的建立及糖尿病并发症相关指标测定[J].实验动物与比较医学,2003.23(2):79-82.
[8]熊昕,隆敏,蔡雷琴,等.一种新型的降糖药物——SGLT2抑制剂研究进展[J].重庆医科大学学报,2016(11):1172-1176.