KLF11通过抑制磷酸烯醇式丙酮酸羧激酶（PEPCK-C）的表达参与小鼠肝脏葡萄糖代谢。
Involvement of KLF11 in hepatic glucose metabolism in mice via suppressing of PEPCK-C expression.
作者信息
Zhang Huabing, Chen Qi, Jiao Tao, Cui Anfang, Sun Xiujing, Fang Weijun, Xie Liwei, Liu Yang, Fang Fude, Chang Yongsheng
机构信息
Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, China ; National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
出版信息
PLoS One. 2014 Feb 26;9(2):e89552. doi: 10.1371/journal.pone.0089552. eCollection 2014.
BACKGROUND
Abnormal hepatic gluconeogenesis is related to hyperglycemia in mammals with insulin resistance. Despite the strong evidences linking Krüppel-like factor 11 (KLF11) gene mutations to development of Type 2 diabetes, the precise physiological functions of KLF11 in vivo remain largely unknown.
RESULTS
In current investigation, we showed that KLF11 is involved in modulating hepatic glucose metabolism in mice. Overexpression of KLF11 in primary mouse hepatocytes could inhibit the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase (cytosolic isoform, PEPCK-C) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), subsequently decreasing the cellular glucose output. Diabetic mice with overexpression of KLF11 gene in livers significantly ameliorated hyperglycemia and glucose intolerance; in contrast, the knockdown of KLF11 expression in db/m and C57BL/6J mice livers impaired glucose tolerance.
CONCLUSIONS
Our data strongly indicated the involvement of KLF11 in hepatic glucose homeostasis via modulating the expression of PEPCK-C.
背景
异常的肝脏糖异生与胰岛素抵抗的哺乳动物的高血糖症相关。尽管有强有力的证据将Krüppel样因子11（KLF11）基因突变与2型糖尿病的发生联系起来，但KLF11在体内的确切生理功能仍 largely未知。
结果
在当前研究中，我们表明KLF11参与调节小鼠肝脏葡萄糖代谢。在原代小鼠肝细胞中过表达KLF11可抑制糖异生基因的表达，包括磷酸烯醇式丙酮酸羧激酶（胞质异构体，PEPCK-C）和过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α），随后降低细胞葡萄糖输出。肝脏中过表达KLF11基因的糖尿病小鼠显著改善了高血糖症和葡萄糖不耐受；相反，在db/m和C57BL/6J小鼠肝脏中敲低KLF11表达损害损害损害葡萄糖耐量受损。
结论
我们的数据强烈表明KLF11通过调节PEPCK-C的表达参与肝脏葡萄糖稳态。
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