The elucidation of antihyperglycemic action mechanism in the liver and pancreatic beta cells of bile acid resin

胆汁酸树脂在肝脏和胰腺β细胞中降血糖作用机制的阐明

• 批准号: 22590989
• 负责人: YAMAKAWA Tadashi
• 金额: $ 2.75万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590989/
• 关键词: 胆汁酸; コレスチミド; 糖尿病; FXR; SHP; 糖脂質代謝; 膵β細胞

The objective of this study was to assess the chronic effects of a bile acid sequestrant, colestimide, on glucose metabolism in type 2 diabetes..Colestimide significantly reduced the elevated fasting blood glucose level, and CA even more markedly reduced fasting blood glucose. A hyperinsulinemic-euglycemic clamp study revealed that colestimide alleviated insulin resistance by suppressing hepatic glucose production and increasing peripheral glucose usage. Colestimide suppressed SHP expression, but enhanced SREBP2 expression. On the other hand, CA increased the expression of SHP and lipogenic enzymes such as ACC and SCD-1, but had no effect on SREBP2.

本研究的目的是评估胆汁酸螯合剂考来替胺对2型糖尿病患者葡萄糖代谢的慢性影响。考来替胺显著降低了升高的空腹血糖水平，CA甚至更显著地降低了空腹血糖。一项高胰岛素-正葡萄糖钳夹研究表明，考来替胺通过抑制肝脏葡萄糖产生和增加外周葡萄糖使用来缓解胰岛素抵抗。考来替胺抑制SHP表达，但增强SREBP 2表达。另一方面，CA增加了SHP和脂肪生成酶如ACC和SCD-1的表达，但对SREBP 2没有影响。