期刊文献+

PRKAA2基因多态性与二甲双胍疗效的相关性研究 被引量:3

Study on correlation of genetic polymorphism of PRKAA2 with metformin response
下载PDF
导出
摘要 目的研究腺苷酸活化蛋白激酶(AMP-activated pro-tein kinase,AMPK)α2亚基基因PRKAA2的单核苷酸多态性(single nucleotide polymorphism,SNP)rs2051040和rs17848595与二甲双胍疗效的关系。方法 2型糖尿病(T2DM)患者32名,服用二甲双胍干预1周(剂量为2000mg·d-1)。治疗前后分别检测空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)。利用聚合酶链式反应-变性梯度凝胶电泳(PCR-DGGE)技术检测PRKAA2基因rs2051040和rs17848595位点的基因型,比较不同基因型患者二甲双胍疗效的差异。结果基因型为野生型患者经过二甲双胍干预之后FPG、TG、TC、LDL-C与治疗前比较差异均有显著性(P<0.05)。基因型为突变型患者经过二甲双胍治疗之后各项生化指标变化无统计学意义(P>0.05)。结论 PRKAA2基因多态性位点rs2051040和rs17848595可以影响二甲双胍的疗效。 Aim To study the single nucleotide poly-morphism ( SNPs ) of AMP-activated protein kinase ( AMPK) α2 subunit gene PRKAA2 ( rs2051040 and rs17848595) and its relationship with metformin response. Methods A total of 32 patients with type 2 diabetes( T2DM) were enrolled. All patients were required to take metformin for 1 week. The serum levels of FPG,TG,TC,LDL-C,HDL-C were assayed before and after therapy. The gene polymorphism of PRKAA2 was analyzed by PCR-DGGE,the effects of metformin were compared between patients with different phenotypes. Results FPG,TG,TC,LDL-C were significantly improved after therapy in wild genotype carriers( P〈0. 05) . The biochemical indexs were not significantly different in mutant genotype carriers after therapy with metformin( P〈0. 05) . Conclusion The results of this study suggest that PRKAA2 polymorphism may be associated with metformin treatment effects in T2DM patients.
出处 《中国药理学通报》 CAS CSCD 北大核心 2010年第8期1041-1044,共4页 Chinese Pharmacological Bulletin
基金 国家自然科学基金资助项目(No30660211) 新疆乌鲁木齐市科技计划项目(NoG07231001)
关键词 多态性 单核苷酸 PRKAA2 二甲双胍 2型糖尿病 DGGE polymorphism single nucleotide PR- KAA2 metformin type 2 diabetes mellitus DGGE
  • 相关文献

参考文献14

  • 1Musi N.AMP-activated protein kinase and type 2 diabetes[J].Curr Med Chem,2006,13(5):583-9.
  • 2葛斌,谢梅林,顾振纶,周文轩,郭次仪.AMPK作为治疗2型糖尿病新靶点的研究进展[J].中国药理学通报,2008,24(5):580-583. 被引量:18
  • 3Misra P.AMP-activated protein kinase:a next generation target for total metabolic control[J].Expert Opin Ther Targets,2008,12(1):91-100.
  • 4Zou M H,Kirkpatrick S S,Davis B J,et al.Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo[J].J Biol Chem,2004,279(42):43940-51.
  • 5Musi N,Hirshman M F,Nygren J,et al.Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes[J].Diabetes,2002,51:2074-81.
  • 6Zang M,Zuccoll O A,Hou X,et al.AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin resistant human HepG2 cells[J].J Biol Chem,2004,279(46):47898-905.
  • 7Hermann L S,Schersten B,Bitzen P O,et al.Therapeutic comparision of metformin and sulphonylurea,alone and in various combinations.A double-blind controlled study[J].Diabetes care,1994,17:1100-9.
  • 8Musi N,Hayashi T,Fujii N,et al.AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle[J].Am J Physiol Endocrinol Metab,2001,280:E677-84.
  • 9Foretz M,Ancellin N,Andreelli F,et al.Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver[J].Diabetes,2005,54:1331-9.
  • 10Viollet B,Andreelli F,Jorgensen S B,et al.Physiological role of AMP-activated protein kinase(AMPK):insights from knockout mouse models[J].Biochem Soc Trans,2003,31:216-9.

二级参考文献34

  • 1刘长锁,申竹芳.游离脂肪酸与胰岛素抵抗[J].中国药理学通报,2005,21(2):145-149. 被引量:37
  • 2赵励彦,王莉莉,李松.脂肪酸合成酶抑制剂减肥作用机制的研究进展[J].中国药理学通报,2006,22(7):780-784. 被引量:11
  • 3汪茂荣(综述),李蓉(综述),任伟(审校),张素华(审校).AMPK与2型糖尿病关系研究进展[J].内分泌外科杂志,2007,1(2):132-134. 被引量:4
  • 4Kamysheva E P. Insulin resistance in intemal diseases[J]. Klin Med (Mosk) ,2007,85(6) :21 -7.
  • 5Blickle J F, Doucet J, Krummel T, et al. Diabetic nephropathy in the elderly[ J]. Diabetes Metab, 2007,33( 1 ) :40 -55.
  • 6Scott J W, Ross F A, Liu J K, et al. Regulation of AMP-activated protein kinase by a pseudosubstrate sequence on the gamma subunit[J]. EMBO J,2007,26(3) :806 - 15.
  • 7Stapleton D, Mitchelhill K I, Gao G, et al. Mammalian AMP-activated protein kinase subfamily [ J ]. J Biol Chem, 1996,271 (2) : 611 -4.
  • 8Hardie D G, Hawley S A, Scott J W. AMP-activated protein kinase-development of the energy sensor concept [ J ]. J Physiol, 2006,574( 1 ) :7 - 15.
  • 9Schimmack G, Defmnzo R A, Musi N. AMP-activated protein kinase: role in metabolism and therapeutic implications[ J]. Diabetes Obes Metab, 2006,8(6) :591 -602.
  • 10Tamas P, Hawley S A, Clarke R G, et al. Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca^2+ in T lymphocytes[ J]. J Exp Med, 2006,203(7) :1665 - 70.

共引文献17

同被引文献26

引证文献3

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部