Thus, prolonged hyperinsulinaemia and chronic hyperglycemia, along with increased ROS and RNS levels, are hypothesized to influence insulin receptor gene expression through the derangement of key transcription factors such as high mobility group AT-hook 1 (HMGA-1) [188]; they may also increase insulin receptor-desensitization, which under normal circumstances is a process under the negative-feedback control [189, 190]. Here, INSR is linked to Hyperglycemia.