Lopez Veronica, Saraff Kumuda, Medh Jheem D
Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262, USA.
Biochem Biophys Res Commun. 2009 Nov 6;389(1):34-9. doi: 10.1016/j.bbrc.2009.08.081. Epub 2009 Aug 19.
Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-gamma) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-gamma activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-gamma in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted in a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.
噻唑烷二酮类药物（TZDs）是用于治疗2型糖尿病的合成降糖药。TZDs作用于过氧化物酶体增殖物激活受体γ（PPAR-γ），并改善全身胰岛素敏感性。特定组织对TZDs作用的贡献，或PPAR-γ激活的下游效应，尚不完全清楚。我们利用大鼠骨骼肌细胞系（L6细胞）证明TZDs可直接作用于肌肉细胞中的PPAR-γ。TZDs处理导致L6细胞中脂蛋白脂肪酶（LPL）表达显著受抑制。这种抑制与葡萄糖摄取增加相关。使用小干扰RNA（siRNA）下调LPL的信使核糖核酸（mRNA）和蛋白质水平，导致胰岛素依赖性葡萄糖摄取有类似增加。因此，LPL下调改善了胰岛素敏感性，且不依赖于TZDs。这一发现为胰岛素抵抗的管理提供了一种新方法。
