Department of Metabolic Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Metabolism. 2013 May;62(5):734-42. doi: 10.1016/j.metabol.2012.10.015. Epub 2012 Nov 26.
Alpha-glucosidase inhibitors (α-GIs) show various anti-diabetic or anti-obesity effects in addition to the suppression of postprandial hyperglycemia. Based on recent observations that bile acids (BAs) are involved in glucose and energy homeostasis, we examined the ability of miglitol, an α-GI, to influence BA metabolism and ameliorate insulin resistance and obesity.
MATERIALS/METHODS: NSY mice, representing an obese type 2 diabetic model, were fed with a high-fat diet and treated with miglitol for 4 or 12 weeks. BAs were quantified in feces, blood from the portal vein or the vena cava and in the liver. The gene expression of type 2 iodothyronine deiodinase (D2) in brown adipose tissues, gluconeogenetic enzymes in the liver and adipokines in epididymal fat was measured, and portal blood glucagon-like peptide-1 (GLP-1) levels, body weight changes, glucose tolerance along with insulin sensitivity were evaluated.
Miglitol significantly increased BAs in both feces and portal blood while the hepatic BA level was reduced. The drug clearly enhanced active GLP-1 secretion into the portal blood and there was a good positive correlation between the active GLP-1 levels and portal blood BA concentrations. D2 expression in brown adipose tended to increase in association with the elevated BA concentrations. Miglitol ameliorated body weight gain, glucose intolerance, insulin resistance and inflammatory adipokine upregulation that were induced by a high-fat diet.
Collectively, miglitol substantially affects BA regulation in mice and this novel finding may explain in part the known favourable effects of the drug on diabetes and obesity.
α-葡萄糖苷酶抑制剂（α-GIs）除了抑制餐后高血糖外，还具有各种抗糖尿病或抗肥胖作用。基于最近观察到胆汁酸（BAs）参与葡萄糖和能量稳态的事实，我们研究了米格列醇（一种α-GI）影响 BA 代谢并改善胰岛素抵抗和肥胖的能力。
材料/方法：代表肥胖 2 型糖尿病模型的 NSY 小鼠喂食高脂肪饮食，并接受米格列醇治疗 4 或 12 周。粪便、门静脉或腔静脉血液和肝脏中的 BA 进行定量分析。测量棕色脂肪组织中 2 型碘甲状腺原氨酸脱碘酶（D2）的基因表达、肝脏中的糖异生酶和附睾脂肪中的脂肪因子，并评估门静脉血胰高血糖素样肽-1（GLP-1）水平、体重变化、葡萄糖耐量以及胰岛素敏感性。
米格列醇显著增加粪便和门静脉血液中的 BA，而肝脏 BA 水平降低。该药物明显增强了活性 GLP-1 向门静脉血液中的分泌，并且活性 GLP-1 水平与门静脉血液 BA 浓度之间存在良好的正相关。与升高的 BA 浓度相关，棕色脂肪组织中的 D2 表达趋于增加。米格列醇改善了高脂肪饮食引起的体重增加、葡萄糖不耐受、胰岛素抵抗和炎症脂肪因子上调。
总的来说，米格列醇可显著影响小鼠的 BA 调节，这一新发现可能部分解释了该药物对糖尿病和肥胖的已知有利影响。
