Oana Fumiki, Takeda Hiroo, Matsuzawa Akane, Akahane Satoshi, Isaji Masayuki, Akahane Masuo
Division of Discovery Research, Kissei Pharmaceutical Co., Ltd., 4365-1, Hotaka, Nagano, 399-8304, Japan.
Eur J Pharmacol. 2005 Jul 25;518(1):71-6. doi: 10.1016/j.ejphar.2005.06.004.
Our aim was to determine the effect of a beta3-adrenoceptor agonist on plasma adiponectin levels and on the level of expression of mRNA for adiponectin, adiponectin receptor 1, and adiponectin receptor 2 in db/db mice. Two weeks' oral administration of CL-316,243 led to decreased plasma levels of hemoglobin A1c, glucose, insulin, triglyceride and free fatty acid, and to an increased plasma adiponectin levels. It also improved insulin resistance in the oral glucose tolerance test. Adiponectin mRNA expression was significantly higher in the CL-316,243-treatment group than in the control group in epididymal white adipose tissue but not in brown adipose tissue, soleus muscle or liver. Adiponectin receptor 2 mRNA expression was significantly lower only in the liver of the CL-316,243-treatment group (versus the control group). These results suggest that the increased plasma adiponectin levels seen in db/db mice treated with this beta3-adrenoceptor agonist induce a down-regulation of adiponectin receptor 2 mRNA expression specifically in the liver.
我们的目的是确定β3-肾上腺素能受体激动剂对db/db小鼠血浆脂联素水平以及脂联素、脂联素受体1和脂联素受体2的mRNA表达水平的影响。口服CL-316,243两周导致血红蛋白A1c、葡萄糖、胰岛素、甘油三酯和游离脂肪酸的血浆水平降低,以及血浆脂联素水平升高。在口服葡萄糖耐量试验中,它还改善了胰岛素抵抗。在附睾白色脂肪组织中,CL-316,243治疗组的脂联素mRNA表达明显高于对照组,但在棕色脂肪组织、比目鱼肌或肝脏中则不然。脂联素受体2 mRNA表达仅在CL-316,243治疗组的肝脏中显著低于(对照组)。这些结果表明,在用这种β3-肾上腺素能受体激动剂治疗的db/db小鼠中观察到的血浆脂联素水平升高会特异性地诱导肝脏中脂联素受体2 mRNA表达的下调。