Hyperglycemia and Glycation in Diabetic Complications

Abstract

Diabetes mellitus is a multifactorial disease, classically influenced by genetic determinants of individual susceptibility and by environmental accelerating factors, such as lifestyle. It is considered a major health concern,as its incidence is increasing at an alarming rate, and the high invalidating effects of its long-term complications affect macro- and microvasculature, heart, kidney, eye, and nerves. Increasing evidence indicates that hyperglycemia is the initiating cause of the tissue damage occurring in diabetes, either through repeated acute changes in cellular glucose metabolism, or through the long-term accumulation of glycated biomolecules and advanced glycation end products (AGEs). AGEs represent a heterogeneous group of chemical products resulting from a nonenzymatic reaction between reducing sugars and proteins, lipids, nucleic acids, or a combination of these.The glycation process (glucose fixation) affects circulating proteins (serum albumin, lipoprotein, insulin, hemoglobin),whereas the formation of AGEs implicates reactive intermediates such as methylglyoxal. AGEs form cross-links on long-lived extracellular matrix proteins or react with their specific receptor RAGE, resulting inoxidative stress and proinflammatory signaling implicated in endothelium dysfunction, arterial stiffening, and microvascular complications. This review summarizes the mechanism of glycation and of AGEs formation and the role of hyperglycemia, AGEs, and oxidative stress in the pathophysiology of diabetic complications.

Effect of dietary inclusions of bitter kola seed on geotactic behavior and oxidative stress markers in Drosophila melanogaster

“…The oxidative stress hypothesis of aging has been well reported in various animal models (Forbes, Coughlan, & Cooper, 2008; Negre‐Salvayre, Salvayre, Auge, Pamplona, & Portero‐Otin, 2009). Specifically, there have been several reports implicating ROS generation and oxidative stress in reduced life span in D. melanogaster (Hyrsl, Büyükgüzel, & Büyükgüzel, 2007; Lozinsky, Lushchak, Storey, Storey, & Lushchak, 2012; Lozinsky et al., 2013).…”

Preventive effects of garlic (Allium sativum) on oxidative stress and histopathology of cardiac tissue in streptozotocin-induced diabetic rats

“…Hyperglycemia of diabetes results in the formation of advanced glycation end products (AGEs) and production of reactive oxygen species (ROS) in different cell lines (20). Diabetes also induces oxidative stress by increased level of MDA and also diminished antioxidant enzymes activities including SOD, GPX, CAT (4,26) that is suggested as a mechanism underlying diabetic complications (4).…”

Association between Serum Malondialdehyde and Insulin in Type 2 Diabetes Mellitus in Eastern India

“…The metabolic dysfunctions of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium due to oxidative stress which acts as mediator of insulin resistance and leads to progression of glucose intolerance and diabetes mellitus which may contribute to micro-and macrovascular complications [2,21,22] .…”