Benomar Yacir, Wetzler Sandrine, Larue-Achagiotis Christiane, Djiane Jean, Tomé Daniel, Taouis Mohammed
Neuroendocrinologie Moléculaire de la Prise Alimentaire INRA, Université Paris XI, IBAIC, Bat447, 91405 Orsay, France.
Mol Cell Endocrinol. 2005 Oct 20;242(1-2):59-66. doi: 10.1016/j.mce.2005.07.003.
Leptin resistance contributes to the pathogenesis of common obesity related metabolic diseases, including insulin resistance. However, the relationship between leptin and insulin resistance is not clearly established. Here, we show that induced hyperleptinemia by leptin infusion alters insulin signalling in rat liver. Leptin infusion clearly reduced the insulin or leptin dependent IRS-1/IRS-2 association to p85 regulatory subunit of PI 3-kinase. Leptin infusion also abolished STAT-3 phosphorylation in response to insulin or leptin and similar results were obtained for MAP-kinase phosphorylation. Hypothalamic leptin resistance was also induced by leptin infusion since leptin was unable to induce STAT-3 phosphorylation. These results provide evidence that induced hyperleptinemia can contribute to the onset of insulin resistance at least at the hepatic level.
瘦素抵抗促成包括胰岛素抵抗在内的常见肥胖相关代谢性疾病的发病机制。然而，瘦素与胰岛素抵抗之间的关系尚未明确确立。在此，我们表明通过输注瘦素诱导的高瘦素血症会改变大鼠肝脏中的胰岛素信号传导。输注瘦素明显降低了胰岛素或瘦素依赖性IRS-1/IRS-2与PI 3-激酶的p85调节亚基的结合。输注瘦素还消除了胰岛素或瘦素刺激下的STAT-3磷酸化，并且丝裂原活化蛋白激酶（MAP-激酶）磷酸化也得到了类似结果。输注瘦素还诱导了下丘脑的瘦素抵抗，因为瘦素无法诱导STAT-3磷酸化。这些结果提供了证据，表明诱导的高瘦素血症至少在肝脏水平可促成胰岛素抵抗的发生。
