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Clinical and Physiological Characterization of Elevated Plasma Glucagon-Like Peptide-1 Levels (Hyperglipemia) in a Dipeptidyl Peptidase IV Mutation Carrier

文献类型：期刊论文

作者Zhao, Dandan1; Zhao, Shaoqian1; Wang, Xiao1; Su, Mingbo3; Liu, Wen1; Ma, Qinyun1; Hong, Jie1; Gu, Weiqiong1; Li, Jingya3; Liu, Ruixin1
刊名FRONTIERS IN ENDOCRINOLOGY
出版日期2018-03-05
卷号9
ISSN号1664-2392
关键词dipeptidyl peptidase IV glucagon-like peptide-1 beta-cell function type 2 diabetes incretin effect
DOI10.3389/fendo.2018.00062
文献子类Article
英文摘要The clinical application of dipeptidyl peptidase IV inhibitors (DPP4i) increasing active glucagon-like peptide-1 (AGLP-1) levels has been linked to pancreatitis, pancreatic tumors, and cardiovascular events. However, DPP4 mutations in humans or the long-term outcomes of high glucagon-like peptide-1 (GLP-1) level exposure have not been reported. A trio family with a proband showing an extremely high AGLP-1 level [defined here as hyperglipemia (hyper-glucagon-like peptide-1-emia)] were conducted whole-exome sequencing for potential pathogenic genetic defects. One novel DPP4 mutation, p.V486M (c.1456 G>A), was identified in the proband and showed damaged enzymatic activity of DPP4. Ex vivo functional study further showed that the serum from the proband markedly enhanced insulin production of primary rat islet cells. Furthermore, V486M variant and another eight DPP4 variants were identified in our in-home database and seven showed decreased enzymatic activities than wild-type DPP4, consistent with their alterations in their protein expression levels. Of note, the levels of glucose, lipids, and tumor markers (especially for CA15-3 and CA125), increased gradually in the proband during a 4-year follow-up period, although no abnormal physical symptoms or imaging results were observed at present. The other two old carriers in the pedigree both had type 2 diabetes, and one of them also had hyperlipidemia and myocarditis. We first identified hyperglipemia in a female subject harboring a loss-of-function DPP4 mutation with decreased DPP4 activity. Other sporadic DPP4 mutations verified the low-frequent occurrence of genetic inhibition of DPP4 activity, at least in the Chinese population studied. These results may provide new evidence for evaluation of the potential long-term effects of DPP4i and GLP-1 analogs.
WOS关键词BETA-CELL FUNCTION ; INSULIN ; SECRETION ; CD26 ; THERAPIES ; PANCREATITIS ; INFLAMMATION ; TOLERANCE ; GLUCOSE ; OBESITY
资助项目Fund of National Ministry of Science and Technology for Precision Medicine Research[2016YFC0901200] ; National Natural Science Foundation of China[81522011] ; National Natural Science Foundation of China[81471074] ; National Natural Science Foundation of China[81670797] ; Fund of Shanghai Jiaotong University School of Medicine[20161411] ; Fund of the Shanghai Municipal Education Commission[14SG17] ; Shanghai Education Development Foundation[14SG17]
WOS研究方向Endocrinology & Metabolism
语种英语
出版者FRONTIERS MEDIA SA
WOS记录号WOS:000426684100001
源URL[http://119.78.100.183/handle/2S10ELR8/279858]  
专题国家新药筛选中心
通讯作者Wang, Jiqiu; Zhang, Yifei
作者单位1.SJTUSM, Ruijin Hosp, Natl Key Lab Med Genomes, China Natl Res Ctr Metab Dis,Dept Endocrinol & Me, Shanghai, Peoples R China;
2.SJTUSM, CAS, SIBS, Inst Hlth Sci, Shanghai, Peoples R China
3.Chinese Acad Sci, SIMM, Natl Ctr Drug Screening, Shanghai, Peoples R China;
推荐引用方式
GB/T 7714		 Zhao, Dandan,Zhao, Shaoqian,Wang, Xiao,et al. Clinical and Physiological Characterization of Elevated Plasma Glucagon-Like Peptide-1 Levels (Hyperglipemia) in a Dipeptidyl Peptidase IV Mutation Carrier[J]. FRONTIERS IN ENDOCRINOLOGY,2018,9.
APA Zhao, Dandan.,Zhao, Shaoqian.,Wang, Xiao.,Su, Mingbo.,Liu, Wen.,...&Zhang, Yifei.(2018).Clinical and Physiological Characterization of Elevated Plasma Glucagon-Like Peptide-1 Levels (Hyperglipemia) in a Dipeptidyl Peptidase IV Mutation Carrier.FRONTIERS IN ENDOCRINOLOGY,9.
MLA Zhao, Dandan,et al."Clinical and Physiological Characterization of Elevated Plasma Glucagon-Like Peptide-1 Levels (Hyperglipemia) in a Dipeptidyl Peptidase IV Mutation Carrier".FRONTIERS IN ENDOCRINOLOGY 9(2018).

入库方式： OAI收割

来源：上海药物研究所

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