Hyperglycemia, Hypoglycemia and Dementia: Role of Mitochondria and Uncoupling Proteins

Abstract

Diabetes mellitus is one of the most prevalent chronic diseases. Since glucose is the main fuel of the brain, its levels should be maintained within a narrow range to ensure normal brain function. Indeed, the literature shows that uncontrolled blood glucose levels, whether too high or too low, impact brain structure and function potentiating cognitive impairment. Uncoupling proteins (UCPs) are a family of mitochondrial anion carrier proteins located on the inner mitochondrial membrane, and their primary function is to leak protons from the intermembrane space into the mitochondrial matrix. The specific role of neuronal UCPs has been widely discussed and although there is no general agreement, there is a strong conviction that these proteins may be involved in the defense against mitochondrial reactive oxygen species (ROS) production and, consequently, protecting against oxidative damage. The generation of ROS is increasingly recognized as playing an important role in diabetes, neurodegenerative disorders and aging where mitochondria are both sources and targets of these reactive species. This review examines the neurodegenerative events associated with diabetes, highlighting the role of hyperglycemia and/or hypoglycemia on cognitive function. The role of mitochondria, neuronal UCPs and their impact in central nervous system will be elucidated. Finally, we will discuss neuronal UCPs as possible therapeutic targets for the treatment of diabetes-associated central complications and neurodegenerative diseases, namely Alzheimer's and Parkinson's diseases.

Pine Bark Extract Protects Against Oxidative Stress Induced By Recurrent Hypoglycemia In Rats.

“…The results of this study are concomitant with the results of the study carried out by the [2] which showed that hypoglycemia may cause an increase in oxidative stress in the brain tissue, and also with the study carried out by [8] which stated that hypoglycemia has led to an increase in the level of MDA with the decreased activity of SOD and GSH content of the brain's cortex and is also consistent with studies conducted by [32], [33], [34] and [35]. The accumulation of large quantities of zinc in neurons as a well as the result of decreased glucose level; has led to an increase in the production of ROS in the nerve cells which led to increased oxidative stress in the brain cortex and the hypothalamus and hypoglycemic coma and brain injury are complications.…”

The mitochondrial O-linked N-acetylglucosamine transferase (mOGT) in the diabetic patient could be the initial trigger to develop Alzheimer disease

“…In neurons, high glucose concentration induces depolarization of the mitochondrial membrane (Liu et al, 2006;Russell et al, 2002), an abnormal mitochondrial activity, as well as impaired bioenergetics status (Fernyhough et al, 2010;Reddy, 2009). As a whole, the aforementioned evidences show the relevance of mitochondria for the evolution of neurodegenerative disorders and aging (Cardoso et al, 2013), however, these events can be inhibited using antioxidants specific for mitochondria (Cao et al, 2012;Moreira et al, 2007).…”

New approach to generating insights for aging research based on literature mining and knowledge integration

“…Therefore, it is likely that these pairs share the same aging-related genes. Moreover, brain-related diseases, such as Neurogenerative disease and Dementia, are closer to the four diseases on the far right-hand side: Hypertension [ 39 , 40 ], Cardiovascular disease [ 41 – 43 ], Diabetes mellitus [ 44 – 46 ], Hyperglycemia [ 47 , 48 ]. This is a demonstration of how our approach can provide overviews of scientific literature to date, and reaffirm scientific results that are understood in the science world.…”