近年来,胰高血糖素样肽-1受体(GLP-1R)基因多态性与妊娠糖尿病(GDM)的关联性逐渐成为研究热点。本综述系统梳理了GLP-1R基因多态性(如rs6923761、rs10305420等位点)对GDM发病风险、胰岛素抵抗及糖代谢紊乱的潜在影响,分析了GLP-1R基因...近年来,胰高血糖素样肽-1受体(GLP-1R)基因多态性与妊娠糖尿病(GDM)的关联性逐渐成为研究热点。本综述系统梳理了GLP-1R基因多态性(如rs6923761、rs10305420等位点)对GDM发病风险、胰岛素抵抗及糖代谢紊乱的潜在影响,分析了GLP-1R基因多态性与GDM的遗传关联研究,结合表观遗传学及多组学分析,探索基于GLP-1R靶点的个体化干预潜力。此项研究领域进展为GDM的早期预测和精准治疗提供了新视角。In recent years, the correlation between glucagon-like peptide-1 receptor (GLP-1R) gene polymorphisms and gestational diabetes mellitus (GDM) has increasingly become a research focus. This review systematically examines the potential effects of GLP-1R gene polymorphisms (e.g., rs6923761, rs10305420 loci) on GDM risk, insulin resistance, and glucose metabolism disorders. It explores genetic association studies between GLP-1R polymorphisms and GDM, integrates epigenetic and multi-omics analyses, and investigates the potential for individualized interventions targeting GLP-1R. Advances in this field provide novel insights for the early prediction and precision treatment of GDM.展开更多
There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1R targeted compounds from Scutel...There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1R targeted compounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuroprotective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1R-dependent manner.Our findings shed light on the importance of GLP-1R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.展开更多
Glucagon-like peptide-1 receptor （GLP-1R） agonists are widely used for treating type 2 diabetes mellitus （T2DM） be- cause of their glucose-lowering and weight-losing effects, and low risk of hypoglycemia. Hence, t...Glucagon-like peptide-1 receptor （GLP-1R） agonists are widely used for treating type 2 diabetes mellitus （T2DM） be- cause of their glucose-lowering and weight-losing effects, and low risk of hypoglycemia. Hence, there is considerable interest in understanding the mechanism underlying the beneficial effects of GLP-I and developing stable and effective GLP-1R agonists. Here, we summarize the presently known mechanism of GLP-I actions, which are mainly through regulating cAMP-PKA signaling pathway; the latest developments in novel clinical GLP-1R agonists are also introduced, which are characterized with multiple properties, such as extended half-life, reduced side-effects, lower production costs and more convenient drug dosing mode. The potential risk of GLP-I-based therapeutics, an often-ignored fact, is also discussed.展开更多
Glucagon peptide-like 1（GLP-1）and GLP-1 receptor（GLP-1R）：GLP-1 is an incretin hormone secreted from gut L cells.GLP-1 exerts its action through binding to its specific receptor,GLP-1R,which is a member of the G p...Glucagon peptide-like 1（GLP-1）and GLP-1 receptor（GLP-1R）：GLP-1 is an incretin hormone secreted from gut L cells.GLP-1 exerts its action through binding to its specific receptor,GLP-1R,which is a member of the G protein-coupled receptor superfamily.GLP-1R is reportedly expressed in various organs,such as the liver,kidney,and peripheral tissues.展开更多
文摘近年来,胰高血糖素样肽-1受体(GLP-1R)基因多态性与妊娠糖尿病(GDM)的关联性逐渐成为研究热点。本综述系统梳理了GLP-1R基因多态性(如rs6923761、rs10305420等位点)对GDM发病风险、胰岛素抵抗及糖代谢紊乱的潜在影响,分析了GLP-1R基因多态性与GDM的遗传关联研究,结合表观遗传学及多组学分析,探索基于GLP-1R靶点的个体化干预潜力。此项研究领域进展为GDM的早期预测和精准治疗提供了新视角。In recent years, the correlation between glucagon-like peptide-1 receptor (GLP-1R) gene polymorphisms and gestational diabetes mellitus (GDM) has increasingly become a research focus. This review systematically examines the potential effects of GLP-1R gene polymorphisms (e.g., rs6923761, rs10305420 loci) on GDM risk, insulin resistance, and glucose metabolism disorders. It explores genetic association studies between GLP-1R polymorphisms and GDM, integrates epigenetic and multi-omics analyses, and investigates the potential for individualized interventions targeting GLP-1R. Advances in this field provide novel insights for the early prediction and precision treatment of GDM.
基金funded by the Fundamental Research Funds for the Central Universities(Grant No.:xzd012022099)Natural Science Basic Research Program of Shaanxi(Grant Nos.:2023-JC-ZD-47,and 2023-JC-QN-0921)+2 种基金Research Project of Shaanxi Administration of Traditional Chinese Medicine(Project No.:SZY-KJCYC-2023-008)Research Project of Guangxi Administration of Traditional Chinese Medicine(Project No.:GXZYJ20230711)Basic&Clinical Sciences Integration Innovation Project of Xi'an Jiaotong University(Project No.:YXJLRH2022018).
文摘There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1R targeted compounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuroprotective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1R-dependent manner.Our findings shed light on the importance of GLP-1R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.
基金Supported by the Natural Science Foundation of China(81172971,81222043)the Program for New Century Excellent Talents in University(NECT11-0170)+2 种基金the Municiple Key Technology Program of Wuhan(Wuhan Bureau of Science & Technology,201260523174)the Clinical Research Foundation of the Health Bureau of Wuhan(WX12B06)the Natural Science Foundation of Hubei Province(2013CFB359)
文摘Glucagon-like peptide-1 receptor （GLP-1R） agonists are widely used for treating type 2 diabetes mellitus （T2DM） be- cause of their glucose-lowering and weight-losing effects, and low risk of hypoglycemia. Hence, there is considerable interest in understanding the mechanism underlying the beneficial effects of GLP-I and developing stable and effective GLP-1R agonists. Here, we summarize the presently known mechanism of GLP-I actions, which are mainly through regulating cAMP-PKA signaling pathway; the latest developments in novel clinical GLP-1R agonists are also introduced, which are characterized with multiple properties, such as extended half-life, reduced side-effects, lower production costs and more convenient drug dosing mode. The potential risk of GLP-I-based therapeutics, an often-ignored fact, is also discussed.
基金supported financially by a research grant from National Research Foundation of Korea(NRF-2010-0023627)
文摘Glucagon peptide-like 1（GLP-1）and GLP-1 receptor（GLP-1R）：GLP-1 is an incretin hormone secreted from gut L cells.GLP-1 exerts its action through binding to its specific receptor,GLP-1R,which is a member of the G protein-coupled receptor superfamily.GLP-1R is reportedly expressed in various organs,such as the liver,kidney,and peripheral tissues.
