Liu Xiaoyu, Du Pengyun, Xu Jianing, Wang Wei, Zhang Chenggang
School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Diabetes Metab Syndr Obes. 2024 Oct 29;17:4013-4030. doi: 10.2147/DMSO.S474196. eCollection 2024.
This study aims to assess the therapeutic potential of combining Shen-Ling-Bai-Zhu-San (SLBZS) or prebiotics with intermittent fasting (IF) in type 2 diabetes mellitus (T2DM) mice and to investigate the synergistic effects and underlying mechanisms.
Type 2 diabetic mouse models were induced using high-fat diet (HFD) and streptozotocin (STZ), followed by IF treatment. Mice were then grouped for combined therapy with different doses of SLBZS and prebiotics. Fasting blood glucose (FBG) levels, body weight variations, and oral glucose tolerance tests were assessed to elucidate metabolic alterations. The hepatic and renal parameters were evaluated to determine systemic changes in T2DM mice, while the insulin levels were quantified by ELISA to assess glucose homeostasis. Gut microbiota alterations were examined via 16S rRNA sequencing. Alterations of the genes in relevant signaling pathways were analyzed using RT-qPCR.
IF improved FBG, body weight, insulin levels, and other diabetes indicators. Combined IF with SLBZS or prebiotics yielded similar effects. Furthermore, it ameliorated dyslipidemia and mitigated hepatic and renal parameters in T2DM mice. Pancreatic tissue histopathology showed islet cell restoration post-intervention. IF therapy reduced the abnormally elevated gene expression and increased the abnormally reduced genes. Further analysis indicated that the combination of IF with prebiotics and high doses of SLBZS upregulated the expression of the and genes. Gut microbiota analysis revealed restored diversity and structure, with notable changes in specific bacterial families. At the family level, the contents of and were restored. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) analysis suggested metabolic pathway alterations.
IF improved type 2 diabetic symptoms, with combined SLBZS and prebiotics showing similar effects. IF with high concentration of SLBZS and prebiotics doses upregulated the and genes and had superior effects on gut microbiota compared to IF alone.
本研究旨在评估参苓白术散（SLBZS）或益生元与间歇性禁食（IF）联合应用于2型糖尿病（T2DM）小鼠的治疗潜力，并探究其协同作用及潜在机制。
采用高脂饮食（HFD）和链脲佐菌素（STZ）诱导建立2型糖尿病小鼠模型，随后进行IF治疗。将小鼠分组，采用不同剂量的SLBZS和益生元进行联合治疗。评估空腹血糖（FBG）水平、体重变化及口服葡萄糖耐量试验，以阐明代谢改变。评估肝脏和肾脏参数，以确定T2DM小鼠的全身变化，同时通过酶联免疫吸附测定（ELISA）对胰岛素水平进行定量，以评估葡萄糖稳态。通过16S核糖体RNA（rRNA）测序检查肠道微生物群的改变。使用逆转录定量聚合酶链反应（RT-qPCR）分析相关信号通路中基因的改变。
IF改善了FBG、体重、胰岛素水平及其他糖尿病指标。IF与SLBZS或益生元联合应用产生了相似的效果。此外，它改善了T2DM小鼠的血脂异常，减轻了肝脏和肾脏参数。胰腺组织病理学显示干预后胰岛细胞恢复。IF治疗降低了异常升高的基因表达，并增加了异常降低的基因。进一步分析表明，IF与益生元及高剂量SLBZS联合上调了 和 基因的表达。肠道微生物群分析显示多样性和结构得以恢复，特定细菌家族有显著变化。在家族水平上， 和 的含量得以恢复。通过未观察状态重建的群落系统发育研究（PICRUSt2）分析表明代谢途径发生了改变。
IF改善了2型糖尿病症状，SLBZS和益生元联合应用显示出相似的效果。高浓度SLBZS和益生元剂量的IF上调了 和 基因，与单独使用IF相比，对肠道微生物群具有更好的效果。
