Tiwari Shuchita, 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):1328-37. doi: 10.2174/13816128113199990552.
Diabetes is a complex endocrine/metabolic disease with many related complications including micro-vascular and macrovascular problems such as cardiomyopathy, nephropathy, neuropathy and retinopathy. Generally, type-1 diabetes is caused by autoimmune- mediated destruction of pancreatic beta cells leading to insulin deficiency. This is usually accompanied by dyslipidemia, enhanced hyperglycemia-mediated oxidative stress, endothelial-cell dysfunction and apoptosis. For decades, type-1 diabetes has been traditionally known as insulin-dependent, while type-2 as non-insulin dependent diabetes. However, it is becoming increasingly clear that insulin deficiency and insulin resistance are manifested in both forms of diabetes at different stages. Thus, it may be time revisit the nomenclature and adjust it to reflect these observations of insulin deficiency and insulin resistance in both forms of diabetes to avoid ambiguity when discussing forms of diabetes. Emerging evidence indicates that the heme-oxygenase (HO) system and related products including carbon monoxide, ferritin and biliverdin are capable of suppressing immune/inflammatory response, and abate oxidative stress and apoptosis. More importantly, upregulating the HO-system increases pancreatic beta-cell insulin release and reduce hyperglycemia in different diabetic models. Similarly, carbon monoxide, a product of the HO-catalyzed degradation of heme also enhances insulin production and improves glucose metabolism. Since excessive immune/inflammatory responses coupled to elevated apoptosis are among the cardinal pathophysiological features of type-1 diabetes, this review highlights the role of the HO-system and related products such as carbon monoxide and bilirubin in the modulation of apoptosis and immune response, and the beneficial effects of the HO-system in the pathogenesis of type-1 diabetes and related cardiometabolic complications.
糖尿病是一种复杂的内分泌/代谢疾病，伴有许多相关并发症，包括微血管和大血管问题，如心肌病、肾病、神经病变和视网膜病变。一般来说，1型糖尿病是由自身免疫介导的胰腺β细胞破坏导致胰岛素缺乏引起的。这通常伴有血脂异常、高血糖介导的氧化应激增强、内皮细胞功能障碍和细胞凋亡。几十年来，1型糖尿病传统上被认为是胰岛素依赖型，而2型糖尿病则是非胰岛素依赖型。然而，越来越明显的是，胰岛素缺乏和胰岛素抵抗在两种类型的糖尿病不同阶段均有表现。因此，可能是时候重新审视命名法并进行调整，以反映两种类型糖尿病中胰岛素缺乏和胰岛素抵抗的这些观察结果，从而在讨论糖尿病类型时避免歧义。新出现的证据表明，血红素加氧酶（HO）系统及相关产物，包括一氧化碳、铁蛋白和胆绿素，能够抑制免疫/炎症反应，减轻氧化应激和细胞凋亡。更重要的是，上调HO系统可增加胰腺β细胞胰岛素释放，并降低不同糖尿病模型中的高血糖水平。同样，一氧化碳作为HO催化血红素降解的产物，也能增强胰岛素生成并改善葡萄糖代谢。由于过度的免疫/炎症反应以及细胞凋亡增加是1型糖尿病的主要病理生理特征，本综述重点介绍了HO系统及相关产物（如一氧化碳和胆红素）在调节细胞凋亡和免疫反应中的作用，以及HO系统在1型糖尿病发病机制及相关心脏代谢并发症中的有益作用。
