Glucose binds to amino groups on proteins or to lipids, leading to the generation of weak bonds or Schiff bases by Maillard's reaction. These early nonenzymatic glycosyla-tion products are reversible and are known as Amadori products. Through several oxidative and nonoxidative reactions, including glycoxidation and auto-oxidative glycosylation, they are converted to irreversibly modified cross-linked condensation products of glucose and lysine or arginine residues, so-called advanced glycosylation end products (AGEs). AGEs formation normally occurs at a low rate during the normal aging process, whereas it is accelerated by hyperglycemia; thus plasma levels of AGEs are increased in patients with T1DM and may precede the occurrence of microangiopathy. AGEs carry out their harmful effects by accumulating in tissue and generating ROS. AGEs bind to their respective cellular receptors (RAGEs), activate endothelial cells, monocytes, and mesangial cells, and increase oxidative stress. AGEs have been found in many proteins, such as collagen, albumin, and plasma lipopro-teins, and in lipids. Moreover, they can also increase lipoprotein oxidizability and atherogenicity; they have been demonstrated in atherosclerotic lesions. AGEs can impair the properties of the basement membrane and stimulate the interaction between mononuclear cells and modified tissue; they can cause endothelial dysfunction by inhibiting type IV collagen formation. AGEs can quench NO and lead to the loss of its vasodilatating and antiproliferative properties. It has been shown that serum AGEs concentrations are increased in adolescents and young adults with T1DM and with diabetic retinopathy and nephropathy, and that the severity of diabetic angiopathy correlate with serum levels of AGEs.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.