PDF(Pubmed)
Abstract：
Accumulated evidence shows that melatonin possesses the potential to improve lipid metabolism by modifying gut microbiota and glucose metabolism via regulating the melatonin receptor signaling pathway. However, the contribution of melatonin consumption on glucose homeostasis by affecting gut microbiota has not been investigated in diabetes. In the current work, we investigated the effect of melatonin administration on gut microbiota and glucose homeostasis in db/db mice, a type 2 diabetes model with leptin receptor deficiency. Administration of melatonin through drinking water (at 0.25% and 0.50%) for 12 weeks decreased diabetic polydipsia and polyuria, increased insulin sensitivity and impeded glycemia. The accumulated fecal levels of total short-chain fatty acids (SCFAs) and acetic acid are positively correlated with diabetes-related parameters-homeostasis model assessment of insulin resistance (HOMA-IR) index and fasting blood glucose (FBG) level. The reprogramming of gut microbiota structure and abundance and the reduction of fecal levels of SCFAs, including acetic acid, butyric acid, isovaleric acid, caproic acid, and isobutyric acid, by melatonin may be beneficial for enhancing insulin sensitivity and lowering FBG, which were verified by the results of correlation analysis between acetic acid or total SCFAs and HOMA-IR and FBG. In addition, the melatonin downregulated hepatic genes, including fructose-1,6-bisphosphatase 1, forkhead box O1 alpha, thioredoxin-interacting protein, phosphoenolpyruvate carboxy-kinase (PEPCK), PEPCK1 and a glucose-6-phosphatase catalytic subunit, that responsible for gluconeogenesis support the result that melatonin improved glucose metabolism. Overall, results showed that the melatonin supplementation reduced fecal SCFAs level via reprogramming of gut microbiota, and the reduction of fecal SCFAs level is associated with improved glucose homeostasis in db/db mice.
摘要：
越来越多的证据表明，褪黑素具有通过调节褪黑素受体信号通路改变肠道菌群和葡萄糖代谢来改善脂质代谢的潜力。然而,褪黑素消耗通过影响肠道菌群对葡萄糖稳态的作用尚未在糖尿病中得到研究.在目前的工作中,我们研究了褪黑素给药对db/db小鼠肠道菌群和葡萄糖稳态的影响，2型糖尿病模型与瘦素受体缺乏。通过饮用水（0.25％和0.50％）给药褪黑激素12周减少糖尿病性多饮和多尿，增加胰岛素敏感性和血糖障碍。粪便总短链脂肪酸（SCFA）和乙酸的累积水平与糖尿病相关参数-稳态模型评估胰岛素抵抗（HOMA-IR）指数和空腹血糖（FBG）水平呈正相关。肠道菌群结构和丰度的重编程以及粪便中SCFA水平的降低，包括乙酸,丁酸,异戊酸，己酸,和异丁酸,通过褪黑激素可能有利于增强胰岛素敏感性和降低FBG，通过乙酸或总SCFA与HOMA-IR和FBG的相关性分析结果进行了验证。此外,褪黑素下调肝脏基因，包括果糖-1,6-双磷酸酶1，叉头盒O1α，硫氧还蛋白相互作用蛋白，磷酸烯醇丙酮酸羧基激酶（PEPCK），PEPCK1和葡萄糖-6-磷酸酶催化亚基，负责糖异生的研究支持褪黑激素改善葡萄糖代谢的结果。总的来说,结果表明，补充褪黑素可通过肠道菌群的重编程降低粪便SCFA水平，粪便SCFAs水平的降低与db/db小鼠葡萄糖稳态的改善有关。
