ABSTRACT
The development of type 2 diabetes is usually associated with a combination of insulin resistance in skeletal muscle, fat, and liver and relative impairment of insulin production in pancreatic β-cells. Normal β-cells can compensate for insulin resistance by increasing insulin secretion, but insufficient compensation leads to the onset of glucose intolerance. There is good reason to believe that insulin-secreting β-cells are subject to injury from oxidative stress during development of type 2 diabetes. Several sources of reactive oxygen species (ROS) production exist in cells, for example, the intracellular nonenzymatic glycosylation reaction and the hexosamine pathway. β-cells have a sensitive system, starting with glucokinase, for initiating the response to physiological changes in glucose concentration. Protective effects of antioxidants, scavengers, and overexpression of antioxidant enzymes in transgenic mouse islets suggest that ROS overproduction can lead to manifestations of oxidative stress and apoptosis in β-cells.
