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

我们已经证明AP-18细胞，一种新从03H/He小鼠皮下组织分离的前脂肪细胞系，表达各种脂肪细胞特异性和脂肪细胞？并在胰岛素培养过程中自发分化为成熟脂肪细胞。通过体外培养AP-1 - 8细胞，观察各种糖尿病临床用药对脂联素、GLUT4基因表达及脂联素蛋白生成的影响。格列齐特和格列本脲（磺脲类）、吡格列酮（噻唑烷二酮）和德莱普利（ACE抑制剂）增加了脂联素和GLUT4的基因表达以及脂联素蛋白的产生，而二甲双胍（双胍类）、替莫卡普利和卡托普利（ACE抑制剂）、坎地沙烷（ARB）、多沙唑嗪（α -1阻滞剂）、美洛尔和选择醇（β -1阻滞剂）和甲基半胱氨酸（半胱氨酸衍生物）则没有这种影响。由于已有研究表明磺酰脲刺激脂肪细胞产生脂联素，我们测量了患者血清中脂联素、tnf - α、il - β、IL-6和瘦素等脂肪细胞因子的浓度(n = 14 ？16)用格列齐特或格列苯利胺治疗，观察这些药物在体内的作用。尽管样本量较小，但格列齐特组患者血清脂联素浓度高于格列本利米组患者，血清TN f - α浓度反之亦然。对AP-i8细胞的研究表明，磺酰脲增加了脂联素和GLUT-4基因的表达，并增加了脂联素蛋白的产生。

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.