PPAR与胰岛素抵抗

PPAR即过氧化物酶体增殖物激活受体 ,是核受体超家族成员之一 ,它可以促进脂肪细胞分化 ,在脂肪代谢中起重要作用。近年来随着对胰岛素增敏剂噻唑烷二酮 (TZD)类药物作用机制的深入研究 ,发现PPARγ是该类药物的主要功能受体 ,于是展开了对于PPAR与胰岛素抵抗之间关系的研究。TZD类药物激活PPARγ ,可以改善胰岛素抵抗 ,而在基因敲除的PPARγ+ / -中 ,却发现胰岛素敏感性增加。所以 ,PPAR激活与改善胰岛素抵抗之间不是简单的正相关关系。对二者关系的进一步明确 ,对于以PPAR为靶点寻找更加有效安全的治疗Ⅱ型糖尿病药物具有关键意义

PPAR and insulin resistance

Peroxisome proliferator activated receptor(PPAR), a member of the hormone receptor superfamily, is a key regulating factor in adipocyte differentiation and lipids metabolism. Recently, with the increased understanding of the precise mechanisms of TZD, thiazolidinedione class of insulin sensitizer, PPARγ has also been identified as the major functional receptor for the drugs. In the study of the relationship between PPAR and insulin resistance, considerable gaps appeared. TZD induced activation of PPARγ is known to promote insulin sensitivity. More interestingly, however, PPARγ +/- heterozygous mice were shown to be less susceptible to insulin resistance. These findings suggest that the relationship between PPAR activation and insulin sensitivity improvement is not simplely positively related. A better understanding of the role of PPAR in insulin action system will be critical in developing more efficacious and safe agents that act on PPAR and benefit patients with type 2 diabetes.