Executive Summary : | Chromium has been shown to improve insulin sensitivity and glycemic control in diabetic patients, with some in-vivo studies showing that the pharmacological amount of Cr(III) complex can improve insulin sensitivity in rodent models of type 2 diabetes (T2DM). However, the molecular mechanism behind these actions is not well understood. In subjects with diabetes, glucose concentration becomes surplus, leading to the glycation of several proteins in the bloodstream, including serum transferrin (Tf), which is believed to alter its function in diabetic patients. Tf is responsible for transporting iron from the gut and liver to tissues, binding and transporting chromium from the bloodstream to insulin-sensitive tissues, and controlling the generation of reactive oxygen radical species (ROS) that cause harmful effects on insulin-producing and insulin-sensitive tissues. Under hyperglycemia conditions, like diabetes mellitus (DM), the glycation of Tf can significantly alter its ability to bind and transport iron and chromium from the bloodstream to tissues. The mechanistic insight behind the glycation of Tf in DM alters the mechanisms of iron uptake and release by Tf, which are the normal course of iron metabolism. To understand how glycation of Tf in T2DM alters these mechanisms, a proposed project will evaluate the kinetic mechanisms and characterize transient intermediates formed during iron and chromium uptake and release by glycated and non-glycated Tf under physiological and endosomal conditions. |