Solomon S S, Mishra S K, Cwik C, Rajanna B, Postlethwaite A E
Research Service, VAMC, Memphis, USA.
Horm Metab Res. 1997 Aug;29(8):379-82. doi: 10.1055/s-2007-979059.
Tumor necrosis factor-alpha (TNF-alpha) has recently been implicated as a cause of insulin resistance (IR) in obesity and non-insulin dependent diabetes mellitus (NIDDM). To examine mechanisms involved, we induced IR induced IR in H-411 E cells with graded doses of TNF-alpha and measured the ability of insulin (INS) to stimulate both calmodulin (CaM) mRNA and glucose utilization. With TNF-alpha concentration at 1 ng/ml and 10(4) muU/ml INS, metformin 10 microM and pioglitazone 1.5 microM, reversed the IR induced by TNF-alpha restoring biologic response to 100% of INS effect alone. Furthermore, comparable results were obtained with glucose utilization/oxidation experiments in the H-411 E cells using glucose U-14C, trapping 14CO2 release in a hyamine filter and extracting 14C labelled lipids with Dole's reagent. In condusion, these data add scientific support for the use of both metformin and pioglitazone in treatment of IR in NIDDM patients and support a rationale for use of use of these drugs alone, and in conjuction with oral agents and/or INS treatment.
肿瘤坏死因子-α（TNF-α）最近被认为是肥胖和非胰岛素依赖型糖尿病（NIDDM）中胰岛素抵抗（IR）的一个原因。为了研究其中涉及的机制，我们用不同剂量的TNF-α在H-411 E细胞中诱导IR，并测量胰岛素（INS）刺激钙调蛋白（CaM）mRNA和葡萄糖利用的能力。当TNF-α浓度为1 ng/ml且INS为10(4) μU/ml时，10 μM二甲双胍和1.5 μM吡格列酮可逆转TNF-α诱导的IR，将生物学反应恢复至单独使用INS时效果的100%。此外，在H-411 E细胞中使用U-14C葡萄糖进行葡萄糖利用/氧化实验，用海胺滤器捕获14CO2释放，并使用多尔试剂提取14C标记的脂质，也得到了类似的结果。总之，这些数据为二甲双胍和吡格列酮用于治疗NIDDM患者的IR提供了科学支持，并支持单独使用这些药物以及与口服药物和/或INS治疗联合使用的理论依据。
