Behind beta cell glucotoxicity: a pivotal role of glycoxidative damage?

This book presents current research from across the globe in the study of Beta-cells, including the induction of pancreatic cancer cell death by elevated concentrations of extracellular zinc; the role of Rab GTPases and their effectors in the insulin secretory pathway of the pancreatic beta cell; In vivo reprogramming of pancreatic A-cells into B-like cells; and the role of glucocortoids, exercise and glucolipotoxicity with regard to stress and pancreatic B-cell function.

Type 2 diabetes, which is the most common form of diabetes, is characterized by hyperglycemia and insulin resistance associated with a progressive deterioration of β-cell function and mass. High blood glucose plays a key role in the development of diabetic complications and may contribute to the progressive β-cell failure. Chronic exposure to high glucose levels increases non enzymatic reactions between aldehydic and amino group of molecules like sugars and proteins, lipids or nucleic acids leading to Advanced Glycation End-Products (AGEs) formation. Accumulation of AGEs is related to the aging process and is boosted by diabetes. Although the pathogenic role of AGEs in microvascular complications of diabetes has been widely investigated and recognized, their role in pancreatic β-cell dysfunction remains to be fully elucidated. Evidence of a direct role of AGEs on pancreatic β-cell dysfunction is discussed in this review. Findings show that exposure to high AGE concentration damages the β-cell functionality affecting insulin production and disturbing the insulin secretion machinery. The studies provide solid evidence that AGEs not only may play a causative role in diabetes complications but may be crucial in the onset and maintenance of it.