A shared comparison of diabetes mellitus and neurodegenerative disorders

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.