Heterogeneity of Metabolic Defects in Type 2 Diabetes and Its Relation to Reactive Oxygen Species and Alterations in Beta-Cell Mass

Abstract

Type 2 diabetes (T2D) is a complex and heterogeneous disease which affects millions of people worldwide. The classification of diabetes is at an interesting turning point and there have been several recent reports on sub-classification of T2D based on phenotypical and metabolic characteristics. An important, and perhaps so far underestimated, factor in the pathophysiology of T2D is the role of oxidative stress and reactive oxygen species (ROS). There are multiple pathways for excessive ROS formation in T2D and in addition, beta-cells have an inherent deficit in the capacity to cope with oxidative stress. ROS formation could be causal, but also contribute to a large number of the metabolic defects in T2D, including beta-cell dysfunction and loss. Currently, our knowledge on beta-cell mass is limited to autopsy studies and based on comparisons with healthy controls. The combined evidence suggests that beta-cell mass is unaltered at onset of T2D but that it declines progressively. In order to better understand the pathophysiology of T2D, to identify and evaluate novel treatments, there is a need for in vivo techniques able to quantify beta-cell mass. Positron emission tomography holds great potential for this purpose and can in addition map metabolic defects, including ROS activity, in specific tissue compartments. In this review, we highlight the different phenotypical features of T2D and how metabolic defects impact oxidative stress and ROS formation. In addition, we review the literature on alterations of beta-cell mass in T2D and discuss potential techniques to assess beta-cell mass and metabolic defects in vivo .

Maternal N-Acetyl Cysteine Intake Improved Glucose Tolerance in Obese Mice Offspring

“…It is well-known [26] that pancreatic β cells are vulnerable to oxidative damage as a result of inherited low activity of antioxidant enzymes in these cells. Thus, metabolic programming that improves the efficiency of the antioxidant defense mechanisms of pancreatic islets might enable β cells to cope more effectively with oxidative stress, driven by chronic hyperglycemia and hyperlipidemia [4,27] and to increase their survival. In addition to its effect on the antioxidant machinery, it is possible that NAC programs the activity of other systems required to resist metabolic stress.…”

“…In addition, exposure to various additional environmental factors increases the susceptibility to develop glucose intolerance and T2D [3]. Oxidative stress is one of these diabetogenic factors, which has a central role in the development and progression of T2D and its associated comorbidities [4,5]. Antioxidant therapy, such as the administration of vitamin E or pentoxifylline, neutralized oxidative stress, improved glucose homeostasis and reduced the severity of nonalcoholic steatohepatitis (NASH) [6][7][8].…”

Cerium Oxide Nanoparticles: Recent Advances in Tissue Engineering

“…In the presence of oxidative stress, the generation of oxidants like ROS augments to excess, as compared to that of endogenous antioxidants, in such a way that cells fail to maintain the balance [ 83 ]. Despite the evidence that a short-term and relatively small upregulation of ROS is of the utmost importance for the redox signaling that plays a pivotal role in multiple processes, including inflammation [ 84 , 85 ] or angiogenesis [ 86 , 87 , 88 ], a long-term and relatively large elevation of ROS leads to the impairment of major cellular macromolecules, deoxyribonucleic acid (DNA), proteins, or lipids that is more likely to induce the formation of many pathological conditions, such as diabetes [ 89 , 90 ] and neurodegenerative diseases [ 91 ].…”

Advances in GLP-1 receptor targeting radiolabeled agent development and prospective of theranostics

“…Prospective in vivo studies for the measurement of beta cell mass in diabetic patients and healthy individuals would potentially allow understanding of underlying disease mechanisms and assignment of individualized treatments. Stratification of patients depending on levels of functional beta cells in pancreas may even impact the diagnosis, as the current major classifications of diabetes (T1D, T2D, gestational diabetes) may be too simplified and do not accurately describe the underlying disease progression 161, 162. Novel sub-categories of diabetes have been proposed based on phenotypical and metabolic characteristics.…”