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Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway

机译:二甲双胍改变上小肠道微生物,影响葡萄糖-Sglt1感应葡糖术途径

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摘要

The gut microbiota alters energy homeostasis. In parallel, metformin regulates upper small intestinal sodium glucose cotransporter-1 (SGLT1), but whether changes of the microbiota or SGLT1-dependent pathways in the upper small intestine mediate metformin action is unknown. Here we report that upper small intestinal glucose sensing triggers an SGLT1-dependent pathway to lower glucose production in rodents. High-fat diet (HFD) feeding reduces glucose sensing and SGLT1 expression in the upper small intestine. Upper small intestinal metformin treatment restores SGLT1 expression and glucose sensing while shifting the upper small intestinal microbiota partly by increasing the abundance of Lactobacillus. Transplantation of upper small intestinal microbiota from metformin-treated HFD rats to the upper small intestine of untreated HFD rats also increases the upper small intestinal abundance of Lactobacillus and glucose sensing via an upregulation of SGLT1 expression. Thus, we demonstrate that metformin alters upper small intestinal microbiota and impacts a glucose-SGLT1-sensing glucoregulatory pathway.
机译:肠道微生物群改变能量稳态。同时,二甲双胍调节上小肠钠-葡萄糖协同转运蛋白-1(SGLT1),但上小肠微生物群或SGLT1依赖性通路的变化是否介导二甲双胍的作用尚不清楚。在这里,我们报告了小肠上部葡萄糖感应触发SGLT1依赖的途径来降低啮齿类动物的葡萄糖生成。高脂饮食(HFD)喂养可降低小肠上部的葡萄糖感应和SGLT1表达。上小肠二甲双胍治疗可恢复SGLT1表达和葡萄糖感应,同时部分通过增加乳酸杆菌的丰度改变上小肠微生物群。将二甲双胍治疗的HFD大鼠的上小肠微生物群移植到未治疗的HFD大鼠的上小肠,也会通过上调SGLT1表达增加上小肠乳酸杆菌的丰度和葡萄糖感应。因此,我们证明二甲双胍改变了小肠上部的微生物群,并影响了葡萄糖-SGLT1敏感的糖调节途径。

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