GLP-1RA及SGLT-2i是ADA和中华医学会糖尿病学分会推荐的新型降糖药物,具有低血糖风险小、兼具心血管保护及降低体重等代谢获益的特点。高尿酸血症是2型糖尿病的独立危险因素,在临床实践中,人们一直在关注预防SUA的升高。据估计,患者SUA...GLP-1RA及SGLT-2i是ADA和中华医学会糖尿病学分会推荐的新型降糖药物,具有低血糖风险小、兼具心血管保护及降低体重等代谢获益的特点。高尿酸血症是2型糖尿病的独立危险因素,在临床实践中,人们一直在关注预防SUA的升高。据估计,患者SUA每升高1 mg/dl,发生T2DM的风险就会增加17%。国内外学者研究结果提示SGLT-2i能兼顾降糖的同时降低SUA水平;最近国外研究显示GLP-1RA还可以降低SUA水平,但仍存在矛盾。国内学者对此研究报告甚少。还需要更多的研究填补此领域的空白,为更好地预防2型糖尿的发生及发展作出贡献。GLP-1RA and SGLT-2i are new hypoglycemic drugs recommended by ADA and Diabetes Branch of Chinese Medical Association, which have the characteristics of low risk of hypoglycemia, metabolic benefits such as cardiovascular protection and weight reduction. Hyperuricemia is an independent risk factor for type 2 diabetes, and much attention has been paid to the prevention of elevated SUA in clinical practice. It is estimated that every 1 mg/dl elevation of patient SUA causes a 17% increase in the risk of developing T2DM. The results of domestic and foreign scholars suggest that SGLT-2i can reduce SUA level while lowering glucose;recent foreign studies show that GLP-1RA can also reduce SUA level, but there are still contradictions. Domestic scholars have few reports on this. More studies are needed to fill the gap in this field to contribute to better prevention of the occurrence and development of type 2 diabetes mellitus.展开更多
Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists(GLP-1RAs)can ameliorate obesity.Our previous studies revealed that(Ex-4)2-Fc,a long-acting GLP-1RA we developed,depends on the leptin ...Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists(GLP-1RAs)can ameliorate obesity.Our previous studies revealed that(Ex-4)2-Fc,a long-acting GLP-1RA we developed,depends on the leptin pathway to treat obesity.However,the mechanisms linking(Ex-4)2-Fc and leptin resistance remain largely unclear.To address this question,we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota,as increasing evidence indicates an important link between the gut microbiota and obesity.This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs.We found that(Ex-4)2-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila(Am).In addition,(Ex-4)2-Fc did not respond well in antibiotic-treated(ATB)Obese mice.Subsequent studies have shown that this defect can be overcome by gavage with Am.In addition,we found that Am enhanced(Ex-4)2-Fc therapy by producing the metabolite inosine.Inosine regulates the macrophage adenosine A2A receptor(A2A)pathway to indirectly reduce leptin levels in adipocytes Thus,elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.展开更多
文摘GLP-1RA及SGLT-2i是ADA和中华医学会糖尿病学分会推荐的新型降糖药物,具有低血糖风险小、兼具心血管保护及降低体重等代谢获益的特点。高尿酸血症是2型糖尿病的独立危险因素,在临床实践中,人们一直在关注预防SUA的升高。据估计,患者SUA每升高1 mg/dl,发生T2DM的风险就会增加17%。国内外学者研究结果提示SGLT-2i能兼顾降糖的同时降低SUA水平;最近国外研究显示GLP-1RA还可以降低SUA水平,但仍存在矛盾。国内学者对此研究报告甚少。还需要更多的研究填补此领域的空白,为更好地预防2型糖尿的发生及发展作出贡献。GLP-1RA and SGLT-2i are new hypoglycemic drugs recommended by ADA and Diabetes Branch of Chinese Medical Association, which have the characteristics of low risk of hypoglycemia, metabolic benefits such as cardiovascular protection and weight reduction. Hyperuricemia is an independent risk factor for type 2 diabetes, and much attention has been paid to the prevention of elevated SUA in clinical practice. It is estimated that every 1 mg/dl elevation of patient SUA causes a 17% increase in the risk of developing T2DM. The results of domestic and foreign scholars suggest that SGLT-2i can reduce SUA level while lowering glucose;recent foreign studies show that GLP-1RA can also reduce SUA level, but there are still contradictions. Domestic scholars have few reports on this. More studies are needed to fill the gap in this field to contribute to better prevention of the occurrence and development of type 2 diabetes mellitus.
基金supported by the 1.3.5 Project for Disciplines of Excellence(No.ZYGD18007)West China Hospital,Sichuan University,the Natural Science Foundation Project of Sichuan Province(No.2022NSFSC1309,China)the National Natural Science Foundation of China(No.82203016).
文摘Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists(GLP-1RAs)can ameliorate obesity.Our previous studies revealed that(Ex-4)2-Fc,a long-acting GLP-1RA we developed,depends on the leptin pathway to treat obesity.However,the mechanisms linking(Ex-4)2-Fc and leptin resistance remain largely unclear.To address this question,we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota,as increasing evidence indicates an important link between the gut microbiota and obesity.This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs.We found that(Ex-4)2-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila(Am).In addition,(Ex-4)2-Fc did not respond well in antibiotic-treated(ATB)Obese mice.Subsequent studies have shown that this defect can be overcome by gavage with Am.In addition,we found that Am enhanced(Ex-4)2-Fc therapy by producing the metabolite inosine.Inosine regulates the macrophage adenosine A2A receptor(A2A)pathway to indirectly reduce leptin levels in adipocytes Thus,elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.
