Song Danjun, Chu Zanbo, Min Luo, Zhen Tan, Li Pengxu, Han Liyuan, Bu Shizhong, yang Julin, Gonzale F J, Liu Aiming
Pharmazie. 2016 Apr;71(4):205-12.
Concurrence of high glucose or diabetes in patients with dyslipidemia is presenting major challenges for clinicians. Although sporadically reported, a rational basis for the use of fibrates for the treatment of dyslipidemia with concurrent metabolic syndrome has not been established.
In this study, wild-type (WT) and Ppara-null (KO) mice were fed a serial gemfibrozil- and fenofibrate-containing diet under the same experimental conditions for 14 days. Glucose level in the blood, glycogen storage in the liver tissues, and the potential toxic responses were assayed. Genes involved in glucose metabolism were determined by quantitative polymerase chain reaction analysis.
Both the blood glucose level and the glycogen content in the liver were down-regulated by gemfibrozil but not by fenofibrate in WT mice, in a dose-dependent manner. This decrement did not occur in KO mice for either fibrate agent. Secondary regulation on the transcription of pyruvate kinase, and gluconolactonase were observed following gemfibrozil treatment, which was differential between WT mice and KO mice.
Gemfibrozil, not fenofibrate, down-regulates systemic glucose level and glycogen storage in the liver dependent on PPARα, suggesting its potential value for treatment of dyslipidemia with concurrent diabetes or high glucose levels.
血脂异常患者并发高血糖或糖尿病给临床医生带来了重大挑战。尽管有零星报道，但贝特类药物用于治疗合并代谢综合征的血脂异常的合理依据尚未确立。
在本研究中，野生型（WT）和过氧化物酶体增殖物激活受体α基因敲除（KO）小鼠在相同实验条件下，连续14天喂食含吉非贝齐和非诺贝特的饮食。检测血液中的葡萄糖水平、肝组织中的糖原储存以及潜在的毒性反应。通过定量聚合酶链反应分析确定参与葡萄糖代谢的基因。
在野生型小鼠中，吉非贝齐以剂量依赖的方式下调血糖水平和肝脏中的糖原含量，而非诺贝特则无此作用。两种贝特类药物在基因敲除小鼠中均未出现这种降低。吉非贝齐治疗后观察到丙酮酸激酶和葡萄糖酸内酯酶转录的二次调节，野生型小鼠和基因敲除小鼠之间存在差异。
吉非贝齐而非非诺贝特可依赖过氧化物酶体增殖物激活受体α下调全身葡萄糖水平和肝脏中的糖原储存，提示其在治疗合并糖尿病或高血糖水平的血脂异常方面具有潜在价值。
