Giannoukakis Nick, Pietropaolo Massimo, Trucco Massimo
Department of Pathology, University of Pittsburgh School of Medicine, PA 15213, USA.
Curr Opin Investig Drugs. 2002 May;3(5):735-51.
Despite the manageability of diabetes mellitus, complications associated with the disorder necessitate novel approaches to prevent immune-mediated impairment and destruction in type 1 diabetes, as well as the pancreatic insufficiency and peripheral resistance to insulin in type 2 diabetes. Islet transplantation is evolving into a clinical reality to treat type 1 diabetics and novel uses of gene engineering technology promise to result in tolerance to auto-, allo- and xenoantigens as well as microenvironment-specific immunosuppression. Through the use of a variety of gene delivery vehides, an increasing number of studies demonstrate the feasibility of shielding islet transplants and surrogate beta cells from immune rejection by the local secretion of immunosuppressive soluble molecules and anti-apoptotic factors. Although the achievements of gene and cell therapy in type 2 diabetes mellitus are less clear, seminal studies demonstrate the relevance of this approach to the treatment and perhaps prevention of the underlying causes of the disease, including obesity and insulin resistance. In this review, we attempt to illustrate pivotal studies demonstrating the suitability of genes and cells as drugs in type 1 and type 2 diabetes mellitus, and also provide some other targets that may be suitable for clinical utility.
尽管糖尿病具有可管理性，但与该疾病相关的并发症需要新的方法来预防1型糖尿病中的免疫介导损伤和破坏，以及2型糖尿病中的胰腺功能不全和外周胰岛素抵抗。胰岛移植正逐渐成为治疗1型糖尿病患者的临床现实，基因工程技术的新应用有望实现对自身抗原、同种异体抗原和异种抗原的耐受性以及微环境特异性免疫抑制。通过使用多种基因递送载体，越来越多的研究表明，通过局部分泌免疫抑制性可溶性分子和抗凋亡因子来保护胰岛移植和替代β细胞免受免疫排斥是可行的。尽管基因和细胞疗法在2型糖尿病中的成果尚不太明确，但开创性研究表明，这种方法与治疗甚至预防该疾病的潜在病因（包括肥胖和胰岛素抵抗）相关。在本综述中，我们试图阐述一些关键研究，这些研究证明了基因和细胞作为药物在1型和2型糖尿病中的适用性，并提供一些可能适用于临床应用的其他靶点。
