Phloretin suppresses carbohydrate-induced GLP-1 secretion via inhibiting short chain fatty acid release from gut microbiome
Phloretin suppresses carbohydrate-induced GLP-1 secretion via inhibiting short chain fatty acid release from gut microbiome
复制标题
根皮素通过抑制肠道微生物群中短链脂肪酸的释放来抑制碳水化合物诱导的 GLP-1 分泌
DOI：
10.1016/j.bbrc.2022.06.069
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发表时间：
2022
影响因子：
3.1
通讯作者：
Miki Takashi
中科院分区：
文献类型：
--
作者：
Ma Yujie;Lee Eunyoung;Yoshikawa Hayato;Noda Tomoe;Miyamoto Junki;Kimura Ikuo;Hatano Ryo;Miki Takashi
我们之前发现，在小鼠中，麦芽糖和α-葡萄糖苷酶抑制剂米格列醇（麦芽糖/米格列醇）联合给药的胰高血糖素样肽1（GLP-1）分泌受到GLUT 2抑制剂根皮素的抑制。此外，麦芽糖/米格列醇通过涉及微生物组产生的短链脂肪酸（SCFA）的机制抑制葡萄糖依赖性促胰岛素多肽（GIP）分泌。然而，根皮素是否通过调节SCFA抑制GLP-1分泌仍不清楚。在这项研究中，我们研究了根皮素对体外和体内微生物组中SCFA释放的影响。在大肠杆菌中，当与麦芽糖/米格列醇一起培养时，根皮素抑制乙酸盐释放到培养基中。在小鼠中，根皮素抑制麦芽糖/米格列醇诱导的门静脉SCFA增加。此外，α-甲基-d-葡萄糖（αMDG）是GLUT 2的不良底物，当与根皮苷联合给药时，可显著增加小鼠的GLP-1分泌，表明GLUT 2对葡萄糖/根皮苷诱导的GLP-1分泌并非必需。αMDG增加门静脉SCFA水平，从而增加GLP-1分泌并抑制小鼠GIP分泌，表明αMDG不是哺乳动物代谢的，而是微生物群代谢的。总之，根皮素可通过抑制微生物组产生的SCFA来抑制麦芽糖/米格列醇诱导的GLP-1分泌。
We previously found that glucagon-like peptide 1 (GLP-1) secretion by co-administration of maltose plus an α-glucosidase inhibitor miglitol (maltose/miglitol) was suppressed by a GLUT2 inhibitor phloretin in mice. In addition, maltose/miglitol inhibited glucose-dependent insulinotropic polypeptide (GIP) secretion through a mechanism involving short chain fatty acids (SCFAs) produced by microbiome. However, it remains unknown whether phloretin suppresses GLP-1 secretion by modulating SCFAs. In this study, we examined the effect of phloretin on SCFA release from microbiomein vitroandin vivo. InEscherichia coli, acetate release into the medium was suppressed by phloretin, when cultured with maltose/miglitol. In mice, phloretin inhibited maltose/miglitol-induced SCFA increase in the portal vein. In addition, alpha methyl-d-glucose (αMDG), a poor substrate for GLUT2, significantly increased GLP-1 secretion when co-administered with phloridzin in mice, suggesting that GLUT2 is not essential for glucose/phloridzin-induced GLP-1 secretion. αMDG increased portal SCFA levels, thereby increasing GLP-1 secretion and suppressing GIP secretion in mice, suggesting that αMDG is metabolizable not for mammals, but for microbiota. In conclusion, phloretin is suggested to suppress maltose/miglitol-induced GLP-1 secretion via inhibiting SCFAs produced by microbiome.