Dufurrena Quinn, Amjad Farhad M, Scherer Philipp E, Weiss Louis M, Nagajyothi Jyothi, Roth Jesse, Tanowitz Herbert B, Kuliawat Regina
Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
Parasitol Res. 2017 Mar;116(3):827-838. doi: 10.1007/s00436-016-5350-5. Epub 2016 Dec 24.
The parasite Trypanosoma cruzi causes a persistent infection, Chagas disease, affecting millions of persons in endemic areas of Latin America. As a result of immigration, this disease has now been diagnosed in non-endemic areas worldwide. Although, the heart and gastrointestinal tract are the most studied, the insulin-secreting β cell of the endocrine pancreas is also a target of infection. In this review, we summarize available clinical and laboratory evidence to determine whether T. cruzi-infection-mediated changes of β cell function is likely to contribute to the development of hyperglycemia and diabetes. Our literature survey indicates that T. cruzi infection of humans and of experimental animals relates to altered secretory behavior of β cells. The mechanistic basis of these observations appears to be a change in stimulus-secretion pathway function rather than the loss of insulin-producing β cells. Whether this attenuated insulin release ultimately contributes to the pathogenesis of diabetes in human Chagas disease, however, remains to be determined. Since the etiologies of diabetes are multifactorial including genetic and lifestyle factors, the use of cell- and animal-based investigations, allowing direct manipulation of these factors, are important tools in testing if reduced insulin secretion has a causal influence on diabetes in the setting of Chagas disease. Long-term clinical investigations will be required to investigate this link in humans.
克氏锥虫这种寄生虫会引发一种持续性感染——恰加斯病，影响拉丁美洲流行地区的数百万人。由于移民，现在全球非流行地区也已诊断出这种疾病。尽管心脏和胃肠道是研究最多的部位，但内分泌胰腺分泌胰岛素的β细胞也是感染目标。在这篇综述中，我们总结了现有的临床和实验室证据，以确定克氏锥虫感染介导的β细胞功能变化是否可能导致高血糖和糖尿病的发生。我们的文献调查表明，人类和实验动物的克氏锥虫感染与β细胞分泌行为的改变有关。这些观察结果的机制基础似乎是刺激-分泌途径功能的改变，而不是产生胰岛素的β细胞的丧失。然而，这种胰岛素释放减弱最终是否会导致人类恰加斯病糖尿病的发病机制，仍有待确定。由于糖尿病的病因是多因素的，包括遗传和生活方式因素，利用基于细胞和动物的研究，能够直接操控这些因素，是检验胰岛素分泌减少在恰加斯病背景下是否对糖尿病有因果影响的重要工具。需要长期的临床研究来调查人类中的这种联系。
