Kagoshima University Graduate School of Medical and Dental Sciences, Department of Gene Therapy and Regenerative Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Expert Opin Biol Ther. 2010 Oct;10(10):1405-14. doi: 10.1517/14712598.2010.512286.
The incidence of diabetes is increasing worldwide, yet current treatments are not always effective for all patient or disease types.
Here, we summarize the biologic and clinical roles of leptin in diabetes, and discuss candidate viral vectors that may be employed in the clinical use of central leptin gene therapy for diabetes.
We discuss how studies on leptin, a regulator of the insulin-glucose axis, have significantly advanced our understanding of the roles of energy homeostasis and insulin resistance in the pathogeneses of metabolic syndrome and diabetes. Recent studies have demonstrated the long-term therapeutic effects of central leptin gene therapy in obesity and diabetes via decreased insulin resistance and increased glucose metabolism. Many of these studies have employed viral vectors, which afford high in vivo gene transduction efficiencies compared with non-viral vectors.
Adeno-associated viral vectors are particularly well suited for central leptin gene therapy owing to their low toxicity and ability to drive transgene expression for extended periods.
糖尿病的发病率在全球范围内不断增加，但目前的治疗方法并不总是对所有患者或疾病类型都有效。
在这里，我们总结了瘦素在糖尿病中的生物学和临床作用，并讨论了可能用于中枢瘦素基因治疗糖尿病的候选病毒载体。
我们讨论了瘦素作为胰岛素-葡萄糖轴的调节剂，如何极大地促进了我们对能量平衡和胰岛素抵抗在代谢综合征和糖尿病发病机制中的作用的理解。最近的研究表明，通过降低胰岛素抵抗和增加葡萄糖代谢，中枢性瘦素基因治疗在肥胖和糖尿病中的长期治疗效果。这些研究中的许多都采用了病毒载体，与非病毒载体相比，病毒载体具有更高的体内基因转导效率。
腺相关病毒载体由于其低毒性和能够延长转基因表达的能力，特别适合用于中枢性瘦素基因治疗。
