Penn State College of Medicine, Department of Pharmacology, Hershey, Pennsylvania 17033, USA.
Adv Exp Med Biol. 2010;688:206-16. doi: 10.1007/978-1-4419-6741-1_14.
Diabetes is a debilitating chronic disease that has no cure and can only be managed by pharmaceutical or nutritional interventions. Worldwide, the incidence of diabetes and diabetic complications is dramatically increasing. This may reflect the incomplete knowledge base underlying the role of inflammatory or nutritional stresses to exacerbate diabetic complications. Despite the knowledge that hyperlipidemia is a cardinal feature of both Type 1 and 2 diabetes, the actual lipid species that contribute to complications such as diabetic nephropathy, retinopathy, neuropathy and cardiovascular disease have not been well defined, or have not elucidated new treatment strategies. Sphingolipids comprise only a fraction of total lipids but a body of evidence has now identified dysfunctional sphingolipid metabolism and/or generation of specific sphingolipid metabolites as contributors to diabetic complications. This review suggests that pharmacological therapies that target dysfunctional sphingolipid metabolism and/or signaling may prove beneficial in decreasing the chronic pathology of hyperglycemia and hyperlipidemia. Moreover, the review suggests that these treatment options may also prove beneficial to ameliorate or delay pancreatic beta cell failure.
糖尿病是一种使人虚弱的慢性疾病，目前无法治愈，只能通过药物或营养干预来控制。在全球范围内，糖尿病及其并发症的发病率正在显著上升。这可能反映了炎症或营养压力在加重糖尿病并发症方面的作用的知识基础不完整。尽管人们知道高脂血症是 1 型和 2 型糖尿病的主要特征，但导致糖尿病肾病、视网膜病变、神经病变和心血管疾病等并发症的实际脂质种类尚未得到很好的定义，也没有阐明新的治疗策略。鞘脂只占总脂质的一小部分，但大量证据表明，鞘脂代谢功能障碍和/或特定鞘脂代谢物的产生是糖尿病并发症的一个因素。这篇综述表明，针对鞘脂代谢功能障碍和/或信号的药理学治疗方法可能有助于减少高血糖和高血脂的慢性病理。此外，该综述还表明，这些治疗选择也可能有助于改善或延缓胰岛β细胞衰竭。
