Radioactive Iodine Therapy and Glucose Tolerance

Abstract

Radioactive iodine therapy is commonly used as an adjuvant therapy in follicular and papillary thyroid carcinoma (PTC) and in the treatment of Graves' disease (GD). The basis of this therapy is the accumulation of radioactive iodine by the sodium-iodide symporter (NIS) in the thyroid gland. Expression of NIS by extrathyroidal tissues such as islets of pancreas has been reported. Radioactive iodine uptake by pancreatic beta-cells can potentially damage these cells. In this study, we discuss the possible associations between radioactive iodine and glucose intolerance. Overall, radioactive iodine uptake by the pancreas may damage beta-cells and predispose patients to glucose intolerance or type 2 diabetes, particularly in patients exposed to radioactive iodine therapy following total thyroidectomy. Further studies are needed to clarify and confirm this association.

Keywords: Glucose Tolerance; Iodine; Pancreas; Radioactive; Sodium-Iodide Symporter.

Fig.1

Glucose enters beta-cells through glucose transporter 2 (GLUT2) and converts to pyruvate in the glycolysis pathway. Pyruvate enters the mitochondrion to be metabolized further and produce ATP. An increased ATP/ADP ratio is necessary for insulin secretion. I-131 (radioactive iodine) enters beta-cells via the sodium-iodide symporter (NIS) and produces reactive oxygen species (ROS). Increased ROS in beta-cells activates uncoupling protein-2 (UCP-2) that decreases the ATP/ADP ratio, leading to suppressed glucose-stimulated insulin secretion (GSIS). Directly, beta-particles interact with essential molecules and disrupt DNA, while indirectly, beta-particles produce ROS by partial reduction of oxygen (O2) and interaction with water molecules. Increased ROS in the nucleus decreases pancreatic duodenal homeobox-1 (PDX-1) expression and activity, and decreases insulin gene expression. TCA; Tricarboxylic acid and VDCC; Voltage-dependent calcium channel.