期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

GLP-1与糖尿病基因治疗 被引量：2

Glucagon-like Peptide-1 and Gene Therapy of Diabetes Mellitus
原文传递
导出
摘要 胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)是由肠道L细胞分泌的一种肽类激素,综合的降糖作用使它在治疗糖尿病方面具有巨大的潜力。但由于二肽酰基肽酶Ⅳ(DPPⅣ)的降解,GLP-1血浆半寿期仅有几分钟,重复多次的给药方式降低了患者的依从性从而限制了它的临床应用。而基因治疗以抵抗DPPⅣ的GLP-1突变基因为基础,通过载体介导,旨在体内达到持续高效表达和延长半寿期的双重疗效。这一方法已成为目前关注的焦点。文章介绍了GLP-1分泌及降解,着重阐述近年来GLP-1在糖尿病基因治疗方面所取得的成果及存在的问题。 Glucagon-like peptide-1 （GLP-1） is a gut-derived peptide hormone secreted from intestinal L-cells. The combined properties of GLP-1 action make it an attractive candidate for treatment of diabetes mellitus. However, circulating GLP-1 has a remarkably short half-life of several minutes, due to its cleavage by dipeptidyl peptidase Ⅳ （DPP Ⅳ ） . Repetitive medication of GLP-1 reduces patient compliance, which limits the therapeutic value of GLP-1 in clinical application. Gene therapy strategy via vector mediation has potential not only in continuous expression of GLP-1 analog in vivo but also in extension of its half-life, which becomes now the focus of attention. The aim of this review is to summarize the recent advances in achievement and insufficiency of GLP-1 gene therapy. In addition, the mechanism how GLP-1 is secreted and degraded will be briefly outlined.
作者 李晓丽 林东子 张志珍
机构地区 广东医学院生物化学与分子生物学教研室
出处 《医学分子生物学杂志》 CAS CSCD 2008年第5期449-453,共5页 Journal of Medical Molecular Biology
基金 广东省自然科学基金(No.7009923)~~
关键词 GLP-1 基因治疗 分泌 糖尿病 glucagon-like peptide-1 gene therapy secretion diabetes mellitus
分类号 Q579.2 [生物学—生物化学] Q789 [生物学—分子生物学]
  • 相关文献

参考文献23

  • 1[1]RANAGANATH L R.Incretins:physiological and therapeutic implications of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1[J].J Clin Pathol,2008,61(4):401-409.
  • 2[2]BURCELIN R,CANI P D,KNAUF C.Glucagon-like peptide-1 and energy homeostasis[J].J Nutr,2007,137(11 Suppl):2534S-2538S.
  • 3[3]HOU J,YAN R,YANG L,et al.High-level expression of fusion protein containing 10 tandem repeated GLP-1 analogs in yeast Pichia pastoris and its biological activityin a diabetic rat model[J].Biosci Biotechnol Biochem,2007,71(6):1462-1469.
  • 4[4]VAHI T P,PATY B W,FALLER B D,et al.Effects of GLP-1-(7-36)NH2,GLP-1-(7-37),and GLP-1-(9-36)NH2 on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans[J].J Clin Endocrinol Metab,2003,88:1772-1779.
  • 5[5]HOLST J J.The physiology of glucagon-like peptide 1[J].Physiol Rev,2007,87 (4):1409-1439.
  • 6[6]FENG X H,LIU X M,ZHOU L H,et al.Expression of glucagon-like peptide-1 in the taste buds of rat circumvallate papillae[J].Acta Histochem,2008,110(2):151-154.
  • 7[7]SHIN Y K,MARTIN B,GOLDEN E,et al.Modulation of taste sensitivity by GLP-1 signaling[J].J Neurochem,2008,106(1):455-463.
  • 8[8]REIMANN F,WARD P S,GRIBBLE F M.Signaling mechanisms underlying the release of glucagon-like peptide[J].Diabetes,2006,55(Suppl.2):S78-S85.
  • 9[9]FLATT P R,BAILEY C J,GREEN B D.Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes[J].Front Biosci,2008,3:3648-3660.
  • 10[10]ELAHI D,EGAN J M,SHANNON R P,et al.GLP-1 (9-36) amide,GLP-1 (7-36) amide,is a glucoregulatory peptide[J].Obesity (Silver Spring),2008,16(7):1501-1509.

二级参考文献22

  • 1[1]FULLER R S,BRAKE A J,THORNER J.Intracellular targeting and structural conservation of a prohormone-processing endoprotease[J].Science,1989,246(4929):482-486.
  • 2[2]HENRICH S,LINDBERG I,BODE W,et al.Proprotein convertase models based on the crystal structures of furin and kexin:explanation of their specificity[J].J Mol Biol,2005,345 (2):211 -227.
  • 3[3]HENRICH S,CAMERON A,BOURENKOV G P,et al.The crystal structure of the proprotein processing proteinase furin explains its stringent specificity[J].Nat Struct Biol,2003,10 (7):520-526.
  • 4[4]NAKAYAMA K.Furin:a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins[J].Biochem J,1997,327 (Pt 3):625-635.
  • 5[5]THOMAS G.Furin at the cutting edge:from protein traffic to embryogenesis and disease[J].Nat Rev Mol Cell Biol,2002,3(10):753-766.
  • 6[6]ANDERSON E D,MOLLOY S S,JEAN F,et al.The ordered and compartment? specific autoproteolytic removal of the furin intramolecular chaperone is required for enzyme activation[J].J Biol Chem,2002,277:12879-12890.
  • 7[7]SALVAS A,BENJANNET S,REUDELHUBER T L,et al.Evidence for proprotein convertase activity in the endoplasmic reticulum/early Golgi[J].FEBS Lett,2005,579 (25):5621-5625.
  • 8[8]BASAK A,LOTFIPOUR F.Modulating furin activity with designed mini-PDX peptides:synthesis and in vitro kinetic evaluation[J].FEBS Lett,2005,579(21):4813-4821.
  • 9[9]KACPRZAK M M,PEINADO J R,THAN M E,et al.Inhibition of furin by polyarginine-containing peptides:nanomolar inhibition by nona-D-arginine[J].J Biol Chem,2004,279 (35):36788-36794.
  • 10[10]SARAC M S,CAMERON A,LINDBERG I.The furin inhibitor hexa-D-arginine blocks the activation of Pseudomonas aeruginosa exotoxin A in vivo[J].Infect Immun,2002,70(12):7136-7139.

共引文献10

同被引文献23

  • 1张万岱,危北海,陈治水,李道本.功能性消化不良的中西医结合诊治方案(草案)[J].中国中西医结合消化杂志,2004,12(6):381-383. 被引量：210
  • 2王宝恩,梁晓梅,贾博琦,陈宝雯,柯美云,林三仁,丁士刚,张锦坤,施礼,张志宏,陈隆典,徐家裕,袁耀宗,阮美娟,刘厚钰,邱德凯,张达荣,李增烈,欧阳钦,王一平,李瑜元,吴惠生,胡家露,姜若兰,王莜如,梁有信.西沙必利治疗功能性消化不良的多中心临床疗效观察[J].中华内科杂志,1995,34(3):180-184. 被引量：113
  • 3张志珍,刘智慧.人胰高血糖素样肽-1突变体的生物学活性研究[J].山西大学学报（自然科学版）,2005,28(3):307-310. 被引量：3
  • 4张志珍,刘智慧,毛积芳.重组人胰高血糖素样肽-1突变体的分离纯化及活性分析[J].中国生物化学与分子生物学报,2005,21(4):510-515. 被引量：1
  • 5林连,史宗强.辨证治疗功能性消化不良56例[J].福建中医药,1996,27(4):3-4. 被引量：16
  • 6EDHOLM T, CEJVAN K, ABDEL-HALIM SM, et al. The incretin hormones GIP and GLP-1 in diabetic rats: effects on insulin secretion and small bowel motility [J]. Neurogastroenterol Motil, 2009, 21(3): 313-321.
  • 7RANAGANATH LR. Incretins: physiological and therapeutic implications of glucose-dependent insulin tropic polypeptide and glucagon-like peptide-1[J]. J ClinPathol, 2008, 61(4): 401-409.
  • 8ZHANG ZZ, YANG SS, DOU H, et al. Experssion, purification, and C-terminal amidation of recombinant hunman glucagon-like peptitide-1[J]. Protein Expr Purif, 2004, 36(2): 292-299.
  • 9FLATT PR, BAILEY C J, GREEN BD. Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes [J]. Front- Bio-sci, 2008, 3: 3648-3660.
  • 10GREEN BD, LANERY KS, IRWIN N, et al. Novel glucagon like peptide-1 (GLP-1) analog (ValS)-GLP-1 results in significant improvements of glucose tolerance and pancreatic beta cell function after 32week daily administration in obese diabetic (ob/ob) mice[J]. J Pharmacol Exp Ther, 2006, 318(2): 914-921.

引证文献2

二级引证文献8

医学分子生物学杂志
2008年 第5期

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