Faculty of Medicine, Menoufia University, Shebin El-kom, Egypt.
Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
J Cell Biochem. 2019 Sep;120(9):14318-14325. doi: 10.1002/jcb.28094. Epub 2018 Dec 19.
Diabetes mellitus (DM), one of the most prevalent metabolic diseases in the world population, is associated with a number of comorbid conditions including obesity, pancreatic endocrine changes, and renal and cardio-cerebrovascular alterations, coupled with peripheral neuropathy and neurodegenerative disease, some of these disorders are bundled into metabolic syndrome. Type 1 DM (T1DM) is an autoimmune disease that destroys the insulin-secreting islet cells. Type 2 DM (T2DM) is diabetes that is associated with an imbalance in the glucagon/insulin homeostasis that leads to the formation of amyloid deposits in the brain, pancreatic islet cells, and possibly in the kidney glomerulus. There are several layers of molecular pathologic alterations that contribute to the DM metabolic pathophysiology and its associated neuropathic manifestations. In this review, we describe the general signature metabolic features of DM and the cross-talk with neurodegeneration. We will assess the underlying molecular key players associated with DM-induced neuropathic disorders that are associated with both T1DM and T2DM. In this context, we will highlight the role of tau and amyloid protein deposits in the brain as well in the pancreatic islet cells, and possibly in the kidney glomerulus. Furthermore, we will discuss the central role of mitochondria, oxidative stress, and the unfolded protein response in mediating the DM-associated neuropathic degeneration. This study will elucidate the relationship between DM and neurodegeneration which may account for the evolution of other neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease as discussed later.
糖尿病（DM）是世界人口中最常见的代谢疾病之一，与许多合并症有关，包括肥胖、胰腺内分泌变化、肾脏和心脑血管改变，以及周围神经病变和神经退行性疾病，其中一些疾病被归为代谢综合征。1 型糖尿病（T1DM）是一种自身免疫性疾病，会破坏胰岛素分泌的胰岛细胞。2 型糖尿病（T2DM）是一种与胰高血糖素/胰岛素平衡失调有关的糖尿病，导致脑、胰岛细胞中淀粉样物质沉积，并可能在肾小球中沉积。有几个分子病理改变的层次，有助于糖尿病的代谢病理生理学及其相关的神经病变表现。在这篇综述中，我们描述了糖尿病的一般特征代谢特征及其与神经退行性变的相互作用。我们将评估与 1 型和 2 型糖尿病相关的糖尿病诱导的神经病变相关的潜在分子关键参与者。在这方面，我们将强调tau 和淀粉样蛋白在大脑以及胰岛细胞中沉积的作用，以及在肾小球中沉积的作用。此外，我们将讨论线粒体、氧化应激和未折叠蛋白反应在介导糖尿病相关神经退行性变中的核心作用。这项研究将阐明糖尿病和神经退行性变之间的关系，这可能解释了其他神经退行性疾病的演变，特别是阿尔茨海默病和帕金森病，如后面所讨论的。
