Mishra Manish, Ndisang Joseph Fomusi
Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5E5.
Curr Pharm Des. 2014;20(9):1370-91. doi: 10.2174/13816128113199990559.
The increased prevalence of diabetes and associated complications presents a major health risk worldwide, and requires an efficient management protocol. Type-1 and type-2 diabetes have several common pathophysiological denominators including hyperglycemia, elevated oxidative stress, increased inflammation and apoptosis. These pathological factors are implicated in the progression and worsening of the disease, and the related cardiometabolic complications associated with it. Despite the advancement in management of type-1 and type-2 diabetes, the high incidence of diabetes and related complications calls for novel therapeutic strategies. Recent findings suggest that the pharmacological modulation of the microsomal heme oxygenase (HO) system may be an important therapeutic avenue to explore. The HO system and related products such as carbon monoxide, bilirubin, biliverdin, biliverdin reductase and ferritin have been shown to abate inflammation, oxidative stress, and apoptosis and reduce hyperglycemia. In addition, the HO system also enhances insulin sensitivity and increase pancreatic beta cell insulin production in experimental models of type-1 and type-2 diabetes. This review is an effort to provide evidence of the regulatory and cytoprotective role of the HO system in type-1 and type-2 diabetes, and will highlight the multifaceted mechanisms implicated in the anti-diabetic effects of the HO system.
糖尿病及其相关并发症患病率的增加在全球范围内构成了重大的健康风险，需要一种有效的管理方案。1型和2型糖尿病有几个共同的病理生理特征，包括高血糖、氧化应激升高、炎症增加和细胞凋亡。这些病理因素与疾病的进展和恶化以及与之相关的心脏代谢并发症有关。尽管1型和2型糖尿病的管理取得了进展，但糖尿病及其相关并发症的高发病率仍需要新的治疗策略。最近的研究结果表明，微粒体血红素加氧酶（HO）系统的药理学调节可能是一个重要的探索治疗途径。HO系统及其相关产物，如一氧化碳、胆红素、胆绿素、胆绿素还原酶和铁蛋白，已被证明可减轻炎症、氧化应激和细胞凋亡，并降低高血糖。此外，在1型和2型糖尿病的实验模型中，HO系统还可增强胰岛素敏感性并增加胰腺β细胞胰岛素分泌。本综述旨在提供HO系统在1型和2型糖尿病中的调节和细胞保护作用的证据，并将突出HO系统抗糖尿病作用的多方面机制。
