Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, Lodz 90-236, Poland.
Molecules. 2013 Nov 7;18(11):13769-811. doi: 10.3390/molecules181113769.
Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amido)amine (PAMAM) dendrimers (G2, G3 and G4) have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer's disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia.
糖尿病是以高血糖为特征的疾病，会给全球人类带来各种大血管和微血管并发症的负担。虽然外源性胰岛素和其他药物可以控制和有时预防各种与糖尿病相关的后遗症，但在糖尿病患者中仍经常遇到许多糖尿病并发症。因此，需要安全有效的降血糖药物，为治疗糖尿病提供替代或复合选择。近年来，由于其作为抗糖化和抗碳化剂的保护价值，氨基端聚（酰胺）胺（PAMAM）树枝状大分子（G2、G3 和 G4）受到关注，可用于限制生物大分子的非酶修饰。本文重点详细介绍我们自己的数据以及可用文献中关于 PAMAM 树枝状大分子的毒性、药理学性质和整体用途的信息。本报告特别关注它们在控制不佳的糖尿病及其并发症中的治疗用途，但也关注其他情况，如阿尔茨海默病，其中这种非酶修饰可能是病理生理机制的基础。本文还展示了树枝状大分子给药对糖尿病动物的总生存率以及对糖基化、糖基氧化、血脑屏障和细胞生物能量学的影响。最后，我们批判性地讨论了在治疗慢性高血糖引起的代谢紊乱时使用 PAMAM 树枝状大分子的潜在优缺点。
