Screening of clinical medicines for effects on gene expressions and protein productions of adipocytokines by using a newly-isolated preadipocyte line

我们已经表明，AP-18细胞，新分离的前脂肪细胞系从皮下组织的03 H/He小鼠，表达各种脂肪细胞特异性和脂肪细胞？本研究以AP-18细胞为研究对象，观察了临床常用的糖尿病药物对脂联素、葡萄糖转运蛋白4基因表达及脂联素蛋白产生的影响。格列齐特和格列本脲（磺脲类），吡格列酮（噻唑烷二酮）和地拉普利（ACE抑制剂）增加脂联素和GLUT 4的基因表达以及脂联素蛋白质的产生，而二甲双胍（双胍）、替莫普利和卡托普利（ACE抑制剂）、坎地沙坦（ARB）、多沙唑嗪（α-i阻滞剂），美托洛尔和selectol（β-1阻滞剂）和甲基半胱氨酸因为已经表明磺酰脲刺激脂肪细胞产生脂联素，我们检测了14例患者血清中脂肪细胞因子包括脂联素、TNF-α、IL-1-β、IL-6和瘦素的浓度。16)用格列齐特或格列本脲治疗，观察这些药物的体内作用。有一个趋势，血清脂联素浓度高格列齐特比格列本脲治疗的患者，血清TNF-α浓度反之亦然，虽然样本量小，使用AP-18细胞的研究表明，磺酰脲类药物增加脂联素和GLUT-4的基因表达，脂联素蛋白的生产。

We have shown that the AP-18 cell, an preadipocyte line newly isolated from subcutaneous tissue of the 03H/He mouse, expresses various adipocyte-specific and adipocyte?related genes, and spontaneously differentiates to mature adipocyte during culture with insulin.Using AP-1 8 cells in vitro, we observed effects of various clinical medicines used for diabetic patients on gene expressions of adiponectin and GLUT4, and on production of adiponectin protein. Gliclazide and glibenclamide (sulfonylureas), pioglitazone (thiazolidinedione), and delapril (ACE inhibitor) increased gene expressions of adiponectin and GLUT4, and adiponectin protein production, whereas metformin (biguanide), temocapril and captopril (ACE inhibitors), candesartane (ARB), doxazosine (alpha-i blocker), metprolol and selectol (beta-1 blockers), and methylcysteine (cysteinderivative) had no such effects.Because it has been indicated that sulfonylurea stimulates adipocytes to produce adiponectin, we measured serum concentration of adipocytekines including adiponectin, TNF-alpha, IL-i-beta, IL-6 and leptin in patients (n = 14 ? 16) treated with gliclazide or glibenclimide to observe in vivo effects of these medicines. There was a tendency that serum adiponecitn concentration was higher in patients treated with gliclazide than those with glibenclimide, and serum TN F-alpha concentration was vice versa, although sample size was small.The study using AP-i8 cells indicates that sulfonylurea increases gene expressions of adiponectin and GLUT-4, and production of adiponecitn protein.