Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nat Rev Drug Discov. 2012 Sep;11(9):692-708. doi: 10.1038/nrd3757.
Since the discovery of leptin in 1994, we now have a better understanding of the cellular and molecular mechanisms underlying its biological effects. In addition to its established anti-obesity effects, leptin exerts antidiabetic actions that are independent of its regulation of body weight and food intake. In particular, leptin can correct diabetes in animal models of type 1 and type 2 diabetes. In addition, long-term leptin replacement therapy improves glycaemic control, insulin sensitivity and plasma triglycerides in patients with severe insulin resistance due to lipodystrophy. These results have spurred enthusiasm for the use of leptin therapy to treat diabetes. Here, we review the current understanding of the glucoregulatory functions of leptin, emphasizing its central mechanisms of action and lessons learned from clinical studies, and discuss possible therapeutic applications of leptin in the treatment of type 1 and type 2 diabetes.
自 1994 年发现瘦素以来，我们对其生物学效应的细胞和分子机制有了更好的理解。除了已确立的抗肥胖作用外，瘦素还具有抗糖尿病作用，而这种作用与它对体重和食物摄入的调节无关。特别是，瘦素可以纠正 1 型和 2 型糖尿病动物模型中的糖尿病。此外，长期的瘦素替代治疗可改善由于脂肪营养不良而导致严重胰岛素抵抗的患者的血糖控制、胰岛素敏感性和血浆甘油三酯。这些结果激发了人们对使用瘦素治疗来治疗糖尿病的热情。在这里，我们回顾了瘦素对糖调节功能的现有认识，强调了其作用的中枢机制以及从临床研究中吸取的经验教训，并讨论了瘦素在治疗 1 型和 2 型糖尿病中的可能治疗应用。
